Variant rs36204974 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000135.4(FANCA):c.1826+30_1826+31insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 1,598,144 control chromosomes in the GnomAD database, including 5,628 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 423 hom., cov: 30)

Exomes 𝑓: 0.076 ( 5205 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.384

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 -16 ACMG points.

BP6

Variant 16-89778770-T-TAC is Benign according to our data. Variant chr16-89778770-T-TAC is described in ClinVar as [Benign]. Clinvar id is 255242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 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.1826+30_1826+31insGT		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 linkuse as main transcript	c.1826+30_1826+31insGT		intron_variant			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.1826+30_1826+31insGT		intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9086

AN:

151442

Hom.:

422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0380

Gnomad ASJ

AF:

0.0580

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.0262

Gnomad FIN

AF:

0.0617

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.0833

Gnomad OTH

AF:

0.0549

GnomAD3 exomes

AF:

0.0673

AC:

16922

AN:

251406

Hom.:

1018

AF XY:

0.0664

AC XY:

9029

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0587

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.0210

Gnomad FIN exome

AF:

0.0582

Gnomad NFE exome

AF:

0.0768

Gnomad OTH exome

AF:

0.0577

GnomAD4 exome

AF:

0.0758

AC:

109648

AN:

1446584

Hom.:

5205

Cov.:

AF XY:

0.0746

AC XY:

53766

AN XY:

720868

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0562

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0571

Gnomad4 NFE exome

AF:

0.0826

Gnomad4 OTH exome

AF:

0.0803

GnomAD4 genome

AF:

0.0600

AC:

9092

AN:

151560

Hom.:

423

Cov.:

AF XY:

0.0580

AC XY:

4296

AN XY:

74006

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.0380

Gnomad4 ASJ

AF:

0.0580

Gnomad4 EAS

AF:

0.226

Gnomad4 SAS

AF:

0.0270

Gnomad4 FIN

AF:

0.0617

Gnomad4 NFE

AF:

0.0833

Gnomad4 OTH

AF:

0.0552

Alfa

AF:

0.0684

Hom.:

Bravo

AF:

0.0576

Asia WGS

AF:

0.115

AC:

400

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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