rs17227191

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.3408+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,576,166 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 68 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 47 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0340

Publications

2 publications found

Variant links:

COSMIC-nc: COSV104619843

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 16-89746798-A-G is Benign according to our data. Variant chr16-89746798-A-G is described in ClinVar as [Benign]. Clinvar id is 255257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCA	NM_000135.4 link	c.3408+33T>C		intron_variant	Intron 34 of 42	ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 link	c.3408+33T>C		intron_variant	Intron 34 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.3408+33T>C		intron_variant	Intron 34 of 42	1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2638

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00955

GnomAD2 exomes

AF:

0.00565

AC:

1067

AN:

188792

AF XY:

0.00465

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.00479

Gnomad EAS exome

AF:

0.0000725

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00271

AC:

3862

AN:

1423868

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

1801

AN XY:

704994

show subpopulations

African (AFR)

AF:

0.0544

AC:

1766

AN:

32450

American (AMR)

AF:

0.00412

AC:

158

AN:

38372

Ashkenazi Jewish (ASJ)

AF:

0.00553

AC:

141

AN:

25480

East Asian (EAS)

AF:

0.00

AC:

AN:

37588

South Asian (SAS)

AF:

0.00169

AC:

139

AN:

82298

European-Finnish (FIN)

AF:

0.0101

AC:

518

AN:

51124

Middle Eastern (MID)

AF:

0.0107

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.000724

AC:

790

AN:

1091808

Other (OTH)

AF:

0.00489

AC:

289

AN:

59040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

235

470

705

940

1175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0173

AC:

2642

AN:

152298

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1265

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0546

AC:

2271

AN:

41570

American (AMR)

AF:

0.00595

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0136

AC:

144

AN:

10612

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00115

AC:

AN:

68030

Other (OTH)

AF:

0.00945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

128

257

385

514

642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0180

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia complementation group A

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

0.56

(source)

DANN

Benign

0.65

PhyloP100

-0.034

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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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rs17227191

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