Variant 16-89792117-C-G 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.1084-49G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,610,850 control chromosomes in the GnomAD database, including 184,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 24632 hom., cov: 32)

Exomes 𝑓: 0.45 ( 159580 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.109

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:

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 16-89792117-C-G is Benign according to our data. Variant chr16-89792117-C-G is described in ClinVar as [Benign]. Clinvar id is 255230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 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.1084-49G>C		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 linkuse as main transcript	c.1084-49G>C		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.1084-49G>C		intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81801

AN:

151958

Hom.:

24598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.471

GnomAD3 exomes

AF:

0.521

AC:

130698

AN:

250854

Hom.:

38668

AF XY:

0.508

AC XY:

68963

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.665

Gnomad ASJ exome

AF:

0.315

Gnomad EAS exome

AF:

0.984

Gnomad SAS exome

AF:

0.588

Gnomad FIN exome

AF:

0.466

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.452

GnomAD4 exome

AF:

0.451

AC:

657426

AN:

1458778

Hom.:

159580

Cov.:

AF XY:

0.452

AC XY:

327870

AN XY:

725948

show subpopulations

Gnomad4 AFR exome

AF:

0.761

Gnomad4 AMR exome

AF:

0.650

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.980

Gnomad4 SAS exome

AF:

0.587

Gnomad4 FIN exome

AF:

0.458

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.468

GnomAD4 genome

AF:

0.539

AC:

81896

AN:

152072

Hom.:

24632

Cov.:

AF XY:

0.548

AC XY:

40687

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.751

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.322

Gnomad4 EAS

AF:

0.981

Gnomad4 SAS

AF:

0.624

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.443

Hom.:

2997

Bravo

AF:

0.556

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

1.6

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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