rs1800286

Positions:

Variant summary

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

The NM_000135.4(FANCA):c.710-12A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,612,118 control chromosomes in the GnomAD database, including 350,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41010 hom., cov: 32)

Exomes 𝑓: 0.64 ( 309565 hom. )

Consequence

FANCA
NM_000135.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001637

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.95

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

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-89803353-T-C is Benign according to our data. Variant chr16-89803353-T-C is described in ClinVar as [Benign]. Clinvar id is 255269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89803353-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
FANCA	NM_000135.4 linkuse as main transcript	c.710-12A>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000389301.8	NP_000126.2
FANCA	NM_001018112.3 linkuse as main transcript	c.710-12A>G	splice_polypyrimidine_tract_variant, intron_variant		NP_001018122.1
FANCA	NM_001286167.3 linkuse as main transcript	c.710-12A>G	splice_polypyrimidine_tract_variant, intron_variant		NP_001273096.1
FANCA	NM_001351830.2 linkuse as main transcript	c.614-12A>G	splice_polypyrimidine_tract_variant, intron_variant		NP_001338759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 linkuse as main transcript	c.710-12A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000135.4	ENSP00000373952	P1	O15360-1

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

109012

AN:

151996

Hom.:

40949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.917

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.676

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.665

GnomAD3 exomes

AF:

0.699

AC:

175544

AN:

251232

Hom.:

63888

AF XY:

0.692

AC XY:

93963

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.923

Gnomad AMR exome

AF:

0.783

Gnomad ASJ exome

AF:

0.521

Gnomad EAS exome

AF:

0.989

Gnomad SAS exome

AF:

0.796

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.642

GnomAD4 exome

AF:

0.644

AC:

940548

AN:

1460004

Hom.:

309565

Cov.:

AF XY:

0.647

AC XY:

469764

AN XY:

726362

show subpopulations

Gnomad4 AFR exome

AF:

0.926

Gnomad4 AMR exome

AF:

0.773

Gnomad4 ASJ exome

AF:

0.524

Gnomad4 EAS exome

AF:

0.983

Gnomad4 SAS exome

AF:

0.796

Gnomad4 FIN exome

AF:

0.670

Gnomad4 NFE exome

AF:

0.608

Gnomad4 OTH exome

AF:

0.653

GnomAD4 genome

AF:

0.717

AC:

109134

AN:

152114

Hom.:

41010

Cov.:

AF XY:

0.725

AC XY:

53920

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.917

Gnomad4 AMR

AF:

0.695

Gnomad4 ASJ

AF:

0.518

Gnomad4 EAS

AF:

0.986

Gnomad4 SAS

AF:

0.815

Gnomad4 FIN

AF:

0.676

Gnomad4 NFE

AF:

0.595

Gnomad4 OTH

AF:

0.669

Alfa

AF:

0.628

Hom.:

17374

Bravo

AF:

0.729

Asia WGS

AF:

0.900

AC:

3131

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group A

Benign:3

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 08, 2021	- -

Fanconi anemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 18, 2019	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 14, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.5

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.0

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