Variant rs6500452 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000135.4(FANCA):c.1084-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,613,442 control chromosomes in the GnomAD database, including 113,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13553 hom., cov: 32)

Exomes 𝑓: 0.35 ( 99939 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.08

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=-0.89).

BP6

Variant 16-89792097-T-C is Benign according to our data. Variant chr16-89792097-T-C is described in ClinVar as [Benign]. Clinvar id is 255229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCA	NM_000135.4 linkuse as main transcript	c.1084-29A>G		intron_variant		ENST00000389301.8
FANCA	NM_001286167.3 linkuse as main transcript	c.1084-29A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCA	ENST00000389301.8 linkuse as main transcript	c.1084-29A>G		intron_variant		1	NM_000135.4	P1	O15360-1

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61237

AN:

151942

Hom.:

13540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.355

GnomAD3 exomes

AF:

0.418

AC:

105168

AN:

251304

Hom.:

25385

AF XY:

0.408

AC XY:

55378

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.631

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.749

Gnomad SAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.353

AC:

515280

AN:

1461382

Hom.:

99939

Cov.:

AF XY:

0.354

AC XY:

257151

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.513

Gnomad4 AMR exome

AF:

0.612

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.816

Gnomad4 SAS exome

AF:

0.478

Gnomad4 FIN exome

AF:

0.388

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.356

GnomAD4 genome

AF:

0.403

AC:

61295

AN:

152060

Hom.:

13553

Cov.:

AF XY:

0.415

AC XY:

30867

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.505

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.243

Gnomad4 EAS

AF:

0.759

Gnomad4 SAS

AF:

0.501

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.333

Hom.:

5400

Bravo

AF:

0.417

Asia WGS

AF:

0.613

AC:

2133

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia complementation group A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.096

DANN

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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