Variant rs17226337 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.1627-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,592,614 control chromosomes in the GnomAD database, including 504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 40 hom., cov: 32)

Exomes 𝑓: 0.013 ( 464 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.133

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=-0.85).

BP6

Variant 16-89779989-A-G is Benign according to our data. Variant chr16-89779989-A-G is described in ClinVar as [Benign]. Clinvar id is 255238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0845 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.1627-32T>C		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 linkuse as main transcript	c.1627-32T>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.1627-32T>C		intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2180

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00799

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00558

Gnomad SAS

AF:

0.0915

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00930

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0195

AC:

4875

AN:

250046

Hom.:

158

AF XY:

0.0228

AC XY:

3084

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.00521

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.00354

Gnomad SAS exome

AF:

0.0856

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0128

AC:

18467

AN:

1440294

Hom.:

464

Cov.:

AF XY:

0.0151

AC XY:

10820

AN XY:

717984

show subpopulations

Gnomad4 AFR exome

AF:

0.0177

Gnomad4 AMR exome

AF:

0.00649

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.00770

Gnomad4 SAS exome

AF:

0.0831

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.00717

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0144

AC:

2186

AN:

152320

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1138

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0176

Gnomad4 AMR

AF:

0.00798

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00559

Gnomad4 SAS

AF:

0.0915

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.00931

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group A

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 08, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.4

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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