rs587118

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004629.2(FANCG):c.1636+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,613,706 control chromosomes in the GnomAD database, including 171,513 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 12186 hom., cov: 32)

Exomes 𝑓: 0.45 ( 159327 hom. )

Consequence

FANCG
NM_004629.2 splice_region, intron

Scores

Splicing: ADA: 0.00009051

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.479

Variant links:

Genes affected

FANCG (HGNC:3588): (FA complementation group G) 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 G. [provided by RefSeq, Jul 2008]

FANCG 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=-0.65).

BP6

Variant 9-35074920-T-C is Benign according to our data. Variant chr9-35074920-T-C is described in ClinVar as [Benign]. Clinvar id is 259477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-35074920-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCG	NM_004629.2 linkuse as main transcript	c.1636+7A>G		splice_region_variant, intron_variant		ENST00000378643.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCG	ENST00000378643.8 linkuse as main transcript	c.1636+7A>G		splice_region_variant, intron_variant		1	NM_004629.2	P2

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53601

AN:

152010

Hom.:

12180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.392

GnomAD3 exomes

AF:

0.402

AC:

100982

AN:

251416

Hom.:

23864

AF XY:

0.403

AC XY:

54693

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0803

Gnomad AMR exome

AF:

0.501

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.00321

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.502

Gnomad NFE exome

AF:

0.500

Gnomad OTH exome

AF:

0.455

GnomAD4 exome

AF:

0.452

AC:

660467

AN:

1461578

Hom.:

159327

Cov.:

AF XY:

0.448

AC XY:

325966

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0767

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.371

Gnomad4 EAS exome

AF:

0.00406

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.495

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.352

AC:

53603

AN:

152128

Hom.:

12186

Cov.:

AF XY:

0.350

AC XY:

26015

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0909

Gnomad4 AMR

AF:

0.458

Gnomad4 ASJ

AF:

0.371

Gnomad4 EAS

AF:

0.00540

Gnomad4 SAS

AF:

0.235

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.497

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.457

Hom.:

21588

Bravo

AF:

0.338

Asia WGS

AF:

0.137

AC:

481

AN:

3478

EpiCase

AF:

0.487

EpiControl

AF:

0.494

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group G

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 08, 2016	- -

Fanconi anemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Amyotrophic Lateral Sclerosis, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Inclusion Body Myopathy, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

Cadd

Benign

9.8

Dann

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.070

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