Variant rs1800330 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.1226-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,612,996 control chromosomes in the GnomAD database, including 123,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.43 ( 15206 hom., cov: 32)

Exomes 𝑓: 0.37 ( 108522 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.44

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 16-89791556-T-C is Benign according to our data. Variant chr16-89791556-T-C is described in ClinVar as [Benign]. Clinvar id is 255232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89791556-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCA	NM_000135.4 link	c.1226-20A>G		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 link	c.1226-20A>G		intron_variant			NP_001273096.1	O15360-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 link	c.1226-20A>G		intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64622

AN:

151940

Hom.:

15190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.551

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.765

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.376

GnomAD3 exomes

AF:

0.441

AC:

109976

AN:

249494

Hom.:

27758

AF XY:

0.433

AC XY:

58432

AN XY:

134936

show subpopulations

Gnomad AFR exome

AF:

0.560

Gnomad AMR exome

AF:

0.638

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.753

Gnomad SAS exome

AF:

0.567

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.367

AC:

535470

AN:

1460938

Hom.:

108522

Cov.:

AF XY:

0.370

AC XY:

268844

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.562

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.824

Gnomad4 SAS exome

AF:

0.565

Gnomad4 FIN exome

AF:

0.400

Gnomad4 NFE exome

AF:

0.319

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.425

AC:

64691

AN:

152058

Hom.:

15206

Cov.:

AF XY:

0.438

AC XY:

32581

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.551

Gnomad4 AMR

AF:

0.489

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.764

Gnomad4 SAS

AF:

0.597

Gnomad4 FIN

AF:

0.407

Gnomad4 NFE

AF:

0.312

Gnomad4 OTH

AF:

0.381

Alfa

AF:

0.337

Hom.:

8741

Bravo

AF:

0.438

Asia WGS

AF:

0.665

AC:

2312

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

-0.94

CADD

Benign

0.10

DANN

Benign

0.53

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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