chr16-89783072-C-T

Position:

chr16-89783072-C-T

Variant summary

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

The ENST00000389301.8(FANCA):c.1501G>A(p.Gly501Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,612,484 control chromosomes in the GnomAD database, including 164,130 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G501G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.51 ( 21693 hom., cov: 31)

Exomes 𝑓: 0.43 ( 142437 hom. )

Consequence

FANCA
ENST00000389301.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:12O:1

Conservation

PhyloP100: -0.965

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 (MetaRNN=1.1434437E-6).

BP6

Variant 16-89783072-C-T is Benign according to our data. Variant chr16-89783072-C-T is described in ClinVar as [Benign]. Clinvar id is 134244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89783072-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 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.1501G>A	p.Gly501Ser	missense_variant	16/43	ENST00000389301.8	NP_000126.2
FANCA	NM_001286167.3 linkuse as main transcript	c.1501G>A	p.Gly501Ser	missense_variant	16/43		NP_001273096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 linkuse as main transcript	c.1501G>A	p.Gly501Ser	missense_variant	16/43	1	NM_000135.4	ENSP00000373952	P1	O15360-1

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77894

AN:

151732

Hom.:

21654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.846

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.502

AC:

126084

AN:

251152

Hom.:

34613

AF XY:

0.489

AC XY:

66328

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.692

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.337

Gnomad EAS exome

AF:

0.856

Gnomad SAS exome

AF:

0.493

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.428

AC:

625737

AN:

1460634

Hom.:

142437

Cov.:

AF XY:

0.429

AC XY:

311440

AN XY:

726668

show subpopulations

Gnomad4 AFR exome

AF:

0.696

Gnomad4 AMR exome

AF:

0.611

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.845

Gnomad4 SAS exome

AF:

0.501

Gnomad4 FIN exome

AF:

0.546

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.446

GnomAD4 genome

AF:

0.514

AC:

77995

AN:

151850

Hom.:

21693

Cov.:

AF XY:

0.523

AC XY:

38780

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.685

Gnomad4 AMR

AF:

0.526

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.846

Gnomad4 SAS

AF:

0.509

Gnomad4 FIN

AF:

0.566

Gnomad4 NFE

AF:

0.388

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.412

Hom.:

34356

Bravo

AF:

0.521

TwinsUK

AF:

0.398

AC:

1477

ALSPAC

AF:

0.370

AC:

1427

ESP6500AA

AF:

0.680

AC:

2991

ESP6500EA

AF:

0.381

AC:

3277

ExAC

AF:

0.499

AC:

60629

Asia WGS

AF:

0.658

AC:

2288

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group A

Uncertain:1Benign:5

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 19, 2022	- -
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, 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	- -
Uncertain significance, no assertion criteria provided	curation	Leiden Open Variation Database	Feb 28, 2020	Curator: Arleen D. Auerbach. Submitter to LOVD: Nikoletta Selenti. -

not specified

Benign:4Other:1

not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 01, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 01, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 01, 2019	This variant is associated with the following publications: (PMID: 27153395, 23021409, 24286411, 24728327) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.29

DANN

Benign

0.47

DEOGEN2

Benign

0.058

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.024

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.2

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.26

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.024

ClinPred

0.0014

GERP RS

-4.6

Varity_R

0.022

gMVP

0.23

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