rs1800345

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.3240-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,519,736 control chromosomes in the GnomAD database, including 110,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14368 hom., cov: 32)

Exomes 𝑓: 0.36 ( 95672 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.715

Publications

17 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=-0.89).

BP6

Variant 16-89748809-C-T is Benign according to our data. Variant chr16-89748809-C-T is described in ClinVar as Benign. ClinVar VariationId is 255254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCA	NM_000135.4 link	c.3240-42G>A		intron_variant	Intron 32 of 42	ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 link	c.3240-42G>A		intron_variant	Intron 32 of 42		NP_001273096.1	O15360-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 link	c.3240-42G>A		intron_variant	Intron 32 of 42	1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62790

AN:

151836

Hom.:

14350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.367

GnomAD2 exomes

AF:

0.428

AC:

93476

AN:

218474

AF XY:

0.417

show subpopulations

Gnomad AFR exome

AF:

0.555

Gnomad AMR exome

AF:

0.631

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.753

Gnomad FIN exome

AF:

0.403

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.357

AC:

488030

AN:

1367782

Hom.:

95672

Cov.:

AF XY:

0.358

AC XY:

244329

AN XY:

683166

show subpopulations

African (AFR)

AF:

0.551

AC:

17586

AN:

31914

American (AMR)

AF:

0.611

AC:

25259

AN:

41314

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

6264

AN:

25306

East Asian (EAS)

AF:

0.818

AC:

31775

AN:

38838

South Asian (SAS)

AF:

0.479

AC:

39736

AN:

82954

European-Finnish (FIN)

AF:

0.392

AC:

20008

AN:

51100

Middle Eastern (MID)

AF:

0.272

AC:

1469

AN:

5410

European-Non Finnish (NFE)

AF:

0.315

AC:

325285

AN:

1033686

Other (OTH)

AF:

0.361

AC:

20648

AN:

57260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

16743

33486

50228

66971

83714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10974

21948

32922

43896

54870

<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:

0.414

AC:

62862

AN:

151954

Hom.:

14368

Cov.:

AF XY:

0.425

AC XY:

31581

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.542

AC:

22484

AN:

41446

American (AMR)

AF:

0.489

AC:

7471

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

852

AN:

3472

East Asian (EAS)

AF:

0.757

AC:

3898

AN:

5146

South Asian (SAS)

AF:

0.496

AC:

2385

AN:

4808

European-Finnish (FIN)

AF:

0.400

AC:

4224

AN:

10550

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20447

AN:

67946

Other (OTH)

AF:

0.373

AC:

786

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1752

3504

5257

7009

8761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.345

Hom.:

1904

Bravo

AF:

0.430

Asia WGS

AF:

0.615

AC:

2137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 10, 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

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia complementation group A

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.22

(source)

DANN

Benign

0.53

PhyloP100

-0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over