Variant chr16-89746786-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.3408+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 1,578,520 control chromosomes in the GnomAD database, including 5,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 416 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5219 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

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=-0.93).

BP6

Variant 16-89746786-C-T is Benign according to our data. Variant chr16-89746786-C-T is described in ClinVar as [Benign]. Clinvar id is 255259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 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.3408+45G>A		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 linkuse as main transcript	c.3408+45G>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.3408+45G>A		intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9057

AN:

152102

Hom.:

415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0375

Gnomad ASJ

AF:

0.0580

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.0616

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0834

Gnomad OTH

AF:

0.0560

GnomAD3 exomes

AF:

0.0683

AC:

13473

AN:

197154

Hom.:

764

AF XY:

0.0680

AC XY:

7196

AN XY:

105766

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.0574

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.0216

Gnomad FIN exome

AF:

0.0617

Gnomad NFE exome

AF:

0.0807

Gnomad OTH exome

AF:

0.0575

GnomAD4 exome

AF:

0.0794

AC:

113278

AN:

1426300

Hom.:

5219

Cov.:

AF XY:

0.0780

AC XY:

55144

AN XY:

707294

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.0217

Gnomad4 ASJ exome

AF:

0.0565

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.0582

Gnomad4 NFE exome

AF:

0.0869

Gnomad4 OTH exome

AF:

0.0831

GnomAD4 genome

AF:

0.0595

AC:

9064

AN:

152220

Hom.:

416

Cov.:

AF XY:

0.0575

AC XY:

4279

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.0374

Gnomad4 ASJ

AF:

0.0580

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.0270

Gnomad4 FIN

AF:

0.0616

Gnomad4 NFE

AF:

0.0833

Gnomad4 OTH

AF:

0.0563

Alfa

AF:

0.0681

Hom.:

100

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 02, 2019	- -

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

-0.93

CADD

Benign

0.31

DANN

Benign

0.50

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