dbSNP rs11076620: FANCA:c.2602-46T>A (chr16-89765112-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000135.4(FANCA):c.2602-46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 1,606,892 control chromosomes in the GnomAD database, including 5,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 415 hom., cov: 33)

Exomes 𝑓: 0.079 ( 5338 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.214

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-89765112-A-T is Benign according to our data. Variant chr16-89765112-A-T is described in ClinVar as [Benign]. Clinvar id is 255249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCA	NM_000135.4 link	c.2602-46T>A		intron_variant	Intron 27 of 42	ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 link	c.2602-46T>A		intron_variant	Intron 27 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.2602-46T>A		intron_variant	Intron 27 of 42	1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9040

AN:

152070

Hom.:

414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0577

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.0263

Gnomad FIN

AF:

0.0606

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0829

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0672

AC:

16562

AN:

246492

Hom.:

968

AF XY:

0.0663

AC XY:

8857

AN XY:

133586

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0586

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.0211

Gnomad FIN exome

AF:

0.0594

Gnomad NFE exome

AF:

0.0773

Gnomad OTH exome

AF:

0.0573

GnomAD4 exome

AF:

0.0792

AC:

115143

AN:

1454706

Hom.:

5338

Cov.:

AF XY:

0.0776

AC XY:

56166

AN XY:

723874

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0569

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.0580

Gnomad4 NFE exome

AF:

0.0867

Gnomad4 OTH exome

AF:

0.0827

GnomAD4 genome

AF:

0.0594

AC:

9046

AN:

152186

Hom.:

415

Cov.:

AF XY:

0.0575

AC XY:

4282

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.0376

Gnomad4 ASJ

AF:

0.0577

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.0269

Gnomad4 FIN

AF:

0.0606

Gnomad4 NFE

AF:

0.0829

Gnomad4 OTH

AF:

0.0553

Alfa

AF:

0.0670

Hom.:

Bravo

AF:

0.0575

Asia WGS

AF:

0.113

AC:

391

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.43

DANN

Benign

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over