rs1800331

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000135.4(FANCA):c.1143G>T(p.Thr381Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 1,614,114 control chromosomes in the GnomAD database, including 5,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 419 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5305 hom. )

Consequence

FANCA
NM_000135.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -3.99

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 16-89792009-C-A is Benign according to our data. Variant chr16-89792009-C-A is described in ClinVar as [Benign]. Clinvar id is 255231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 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.1143G>T	p.Thr381Thr	synonymous_variant	13/43	ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 linkuse as main transcript	c.1143G>T	p.Thr381Thr	synonymous_variant	13/43		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.1143G>T	p.Thr381Thr	synonymous_variant	13/43	1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.0608

AC:

9247

AN:

152164

Hom.:

418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.0577

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0609

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0833

Gnomad OTH

AF:

0.0565

GnomAD3 exomes

AF:

0.0667

AC:

16775

AN:

251466

Hom.:

993

AF XY:

0.0658

AC XY:

8944

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0587

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.0210

Gnomad FIN exome

AF:

0.0584

Gnomad NFE exome

AF:

0.0767

Gnomad OTH exome

AF:

0.0572

GnomAD4 exome

AF:

0.0789

AC:

115293

AN:

1461832

Hom.:

5305

Cov.:

AF XY:

0.0773

AC XY:

56218

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.0208

Gnomad4 ASJ exome

AF:

0.0570

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.0220

Gnomad4 FIN exome

AF:

0.0572

Gnomad4 NFE exome

AF:

0.0864

Gnomad4 OTH exome

AF:

0.0829

GnomAD4 genome

AF:

0.0608

AC:

9257

AN:

152282

Hom.:

419

Cov.:

AF XY:

0.0587

AC XY:

4368

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0193

Gnomad4 AMR

AF:

0.0362

Gnomad4 ASJ

AF:

0.0577

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.0267

Gnomad4 FIN

AF:

0.0609

Gnomad4 NFE

AF:

0.0833

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0688

Hom.:

569

Bravo

AF:

0.0586

Asia WGS

AF:

0.113

AC:

391

AN:

3478

EpiCase

AF:

0.0746

EpiControl

AF:

0.0724

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 06, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -

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 12, 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, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 06, 2019	- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.015

DANN

Benign

0.28

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

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