16-89762029-A-G

Position:

chr16-89762029-A-G

Variant summary

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

The NM_000135.4(FANCA):c.2779-7T>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 0.0764 in 1,608,136 control chromosomes in the GnomAD database, including 5,674 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 0.060 ( 420 hom., cov: 32)

Exomes 𝑓: 0.078 ( 5254 hom. )

Consequence

FANCA
NM_000135.4 splice_region, intron

Scores

Splicing: ADA: 0.00003180

Clinical Significance

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

Conservation

PhyloP100: 0.0540

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=-0.91).

BP6

Variant 16-89762029-A-G is Benign according to our data. Variant chr16-89762029-A-G is described in ClinVar as [Benign]. Clinvar id is 255250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCA	NM_000135.4 link	c.2779-7T>C		splice_region_variant, intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 link	c.2779-7T>C		splice_region_variant, 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.2779-7T>C		splice_region_variant, intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.0597

AC:

9082

AN:

152124

Hom.:

419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.0580

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0615

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0830

Gnomad OTH

AF:

0.0560

GnomAD3 exomes

AF:

0.0671

AC:

16876

AN:

251470

Hom.:

1009

AF XY:

0.0662

AC XY:

9000

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0582

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.0211

Gnomad FIN exome

AF:

0.0594

Gnomad NFE exome

AF:

0.0768

Gnomad OTH exome

AF:

0.0568

GnomAD4 exome

AF:

0.0781

AC:

113717

AN:

1455894

Hom.:

5254

Cov.:

AF XY:

0.0766

AC XY:

55537

AN XY:

724608

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0566

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.0220

Gnomad4 FIN exome

AF:

0.0581

Gnomad4 NFE exome

AF:

0.0854

Gnomad4 OTH exome

AF:

0.0820

GnomAD4 genome

AF:

0.0597

AC:

9089

AN:

152242

Hom.:

420

Cov.:

AF XY:

0.0578

AC XY:

4304

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.0378

Gnomad4 ASJ

AF:

0.0580

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.0267

Gnomad4 FIN

AF:

0.0615

Gnomad4 NFE

AF:

0.0830

Gnomad4 OTH

AF:

0.0563

Alfa

AF:

0.0688

Hom.:

179

Bravo

AF:

0.0574

EpiCase

AF:

0.0744

EpiControl

AF:

0.0731

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, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
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	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:2

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	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 02, 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

-0.91

CADD

Benign

1.7

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.0020

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