16-89771670-A-G

Variant names:

Variant summary

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

The NM_000135.4(FANCA):c.2151+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,613,336 control chromosomes in the GnomAD database, including 121,852 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14251 hom., cov: 31)

Exomes 𝑓: 0.37 ( 107601 hom. )

Consequence

FANCA
NM_000135.4 splice_region, intron

Scores

Splicing: ADA: 0.00001916

Clinical Significance

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

Conservation

PhyloP100: -1.39

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=-0.9).

BP6

Variant 16-89771670-A-G is Benign according to our data. Variant chr16-89771670-A-G is described in ClinVar as [Benign]. Clinvar id is 255245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89771670-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCA	NM_000135.4 link	c.2151+8T>C		splice_region_variant, intron_variant	Intron 23 of 42	ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 link	c.2151+8T>C		splice_region_variant, intron_variant	Intron 23 of 42		NP_001273096.1	O15360-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 link	c.2151+8T>C		splice_region_variant, intron_variant	Intron 23 of 42	1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62868

AN:

151740

Hom.:

14233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.438

AC:

110023

AN:

251442

Hom.:

27519

AF XY:

0.431

AC XY:

58561

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.520

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.743

Gnomad SAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.365

AC:

533872

AN:

1461478

Hom.:

107601

Cov.:

AF XY:

0.369

AC XY:

268195

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.521

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.817

Gnomad4 SAS exome

AF:

0.568

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.319

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.414

AC:

62938

AN:

151858

Hom.:

14251

Cov.:

AF XY:

0.428

AC XY:

31765

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.487

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.598

Gnomad4 FIN

AF:

0.410

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.374

Alfa

AF:

0.355

Hom.:

6358

Bravo

AF:

0.425

Asia WGS

AF:

0.654

AC:

2273

AN:

3478

EpiCase

AF:

0.306

EpiControl

AF:

0.294

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:5

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.017

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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