Variant 16-89742763-C-T 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.3765+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 1,607,346 control chromosomes in the GnomAD database, including 5,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 410 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5300 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.721

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-89742763-C-T is Benign according to our data. Variant chr16-89742763-C-T is described in ClinVar as [Benign]. Clinvar id is 255262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 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.3765+37G>A		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 linkuse as main transcript	c.3765+37G>A		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.3765+37G>A		intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9024

AN:

151556

Hom.:

409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0580

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.0264

Gnomad FIN

AF:

0.0612

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0831

Gnomad OTH

AF:

0.0565

GnomAD3 exomes

AF:

0.0665

AC:

16690

AN:

251094

Hom.:

969

AF XY:

0.0657

AC XY:

8926

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.0584

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.0209

Gnomad FIN exome

AF:

0.0586

Gnomad NFE exome

AF:

0.0766

Gnomad OTH exome

AF:

0.0564

GnomAD4 exome

AF:

0.0788

AC:

114709

AN:

1455694

Hom.:

5300

Cov.:

AF XY:

0.0773

AC XY:

55979

AN XY:

724286

show subpopulations

Gnomad4 AFR exome

AF:

0.0113

Gnomad4 AMR exome

AF:

0.0211

Gnomad4 ASJ exome

AF:

0.0572

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.0220

Gnomad4 FIN exome

AF:

0.0576

Gnomad4 NFE exome

AF:

0.0864

Gnomad4 OTH exome

AF:

0.0823

GnomAD4 genome

AF:

0.0596

AC:

9031

AN:

151652

Hom.:

410

Cov.:

AF XY:

0.0575

AC XY:

4257

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.0372

Gnomad4 ASJ

AF:

0.0580

Gnomad4 EAS

AF:

0.218

Gnomad4 SAS

AF:

0.0273

Gnomad4 FIN

AF:

0.0612

Gnomad4 NFE

AF:

0.0831

Gnomad4 OTH

AF:

0.0570

Alfa

AF:

0.0436

Hom.:

Bravo

AF:

0.0572

Asia WGS

AF:

0.113

AC:

393

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	Feb 02, 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

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.6

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

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