16-89796026-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000135.4(FANCA):c.894-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,610,696 control chromosomes in the GnomAD database, including 6,090 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 469 hom., cov: 33)

Exomes 𝑓: 0.081 ( 5621 hom. )

Consequence

FANCA
NM_000135.4 splice_region, intron

Scores

Splicing: ADA: 0.00001054

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -3.08

Publications

9 publications found

Variant links:

Genes affected

FANCA (HGNC:3582): (FA complementation group A) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

FANCA Gene-Disease associations (from GenCC):

Fanconi anemia complementation group A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FANCA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 16-89796026-T-C is Benign according to our data. Variant chr16-89796026-T-C is described in ClinVar as Benign. ClinVar VariationId is 255270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000135.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	NM_000135.4	MANE Select	c.894-8A>G		splice_region intron	N/A	NP_000126.2
	FANCA	NM_001286167.3		c.894-8A>G		splice_region intron	N/A	NP_001273096.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FANCA	ENST00000389301.8	TSL:1 MANE Select	c.894-8A>G	splice_region intron	N/A	ENSP00000373952.3
FANCA	ENST00000566409.1	TSL:1	n.*158-8A>G	splice_region intron	N/A	ENSP00000457647.1
FANCA	ENST00000567205.2	TSL:1	n.894-8A>G	splice_region intron	N/A	ENSP00000457027.2

Frequencies

GnomAD3 genomes

AF:

0.0621

AC:

9442

AN:

152118

Hom.:

467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0392

Gnomad ASJ

AF:

0.0590

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.0271

Gnomad FIN

AF:

0.0775

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0838

Gnomad OTH

AF:

0.0574

GnomAD2 exomes

AF:

0.0737

AC:

18515

AN:

251154

AF XY:

0.0719

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.0428

Gnomad ASJ exome

AF:

0.0598

Gnomad EAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.0746

Gnomad NFE exome

AF:

0.0778

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0808

AC:

117915

AN:

1458460

Hom.:

5621

Cov.:

AF XY:

0.0792

AC XY:

57450

AN XY:

725772

show subpopulations

African (AFR)

AF:

0.0116

AC:

386

AN:

33418

American (AMR)

AF:

0.0404

AC:

1808

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

1541

AN:

26114

East Asian (EAS)

AF:

0.171

AC:

6798

AN:

39672

South Asian (SAS)

AF:

0.0227

AC:

1959

AN:

86196

European-Finnish (FIN)

AF:

0.0725

AC:

3867

AN:

53324

Middle Eastern (MID)

AF:

0.0134

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0869

AC:

96335

AN:

1108980

Other (OTH)

AF:

0.0853

AC:

5144

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

5349

10698

16048

21397

26746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3602

7204

10806

14408

18010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0621

AC:

9447

AN:

152236

Hom.:

469

Cov.:

AF XY:

0.0605

AC XY:

4500

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0145

AC:

603

AN:

41552

American (AMR)

AF:

0.0390

AC:

597

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

205

AN:

3472

East Asian (EAS)

AF:

0.241

AC:

1243

AN:

5166

South Asian (SAS)

AF:

0.0280

AC:

135

AN:

4822

European-Finnish (FIN)

AF:

0.0775

AC:

821

AN:

10594

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0838

AC:

5699

AN:

68018

Other (OTH)

AF:

0.0577

AC:

122

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

460

920

1379

1839

2299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0725

Hom.:

360

Bravo

AF:

0.0595

Asia WGS

AF:

0.119

AC:

412

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group A

Benign:5

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 10, 2025

GeneKor MSA

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 02, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23021409)

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.085

(source)

DANN

Benign

0.25

PhyloP100

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000011

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over