Variant rs2159116 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000135.4(FANCA):c.2602-36G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,610,760 control chromosomes in the GnomAD database, including 22,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1477 hom., cov: 33)

Exomes 𝑓: 0.16 ( 21417 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.70

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:

FANCA (HGNC:):

FANCA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-89765102-C-A is Benign according to our data. Variant chr16-89765102-C-A is described in ClinVar as [Benign]. Clinvar id is 255248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCA	NM_000135.4 linkuse as main transcript	c.2602-36G>T		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 linkuse as main transcript	c.2602-36G>T		intron_variant			NP_001273096.1	O15360-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 linkuse as main transcript	c.2602-36G>T		intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18621

AN:

152126

Hom.:

1477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.145

AC:

36116

AN:

248354

Hom.:

3136

AF XY:

0.153

AC XY:

20562

AN XY:

134434

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.0997

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.00334

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.165

AC:

240568

AN:

1458516

Hom.:

21417

Cov.:

AF XY:

0.167

AC XY:

120937

AN XY:

725560

show subpopulations

Gnomad4 AFR exome

AF:

0.0358

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.00182

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.157

GnomAD4 genome

AF:

0.122

AC:

18611

AN:

152244

Hom.:

1477

Cov.:

AF XY:

0.120

AC XY:

8952

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0380

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.174

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.123

Hom.:

423

Bravo

AF:

0.118

Asia WGS

AF:

0.0920

AC:

320

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.3

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

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

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