Variant 7-100682365-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001375765.1(GIGYF1):c.2718C>T(p.Cys906Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,613,464 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 3 hom. )

Consequence

GIGYF1
NM_001375765.1 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0850

Variant links:

Genes affected

GIGYF1 (HGNC:9126): (GRB10 interacting GYF protein 1) This gene encodes a member of the gyf family of adaptor proteins. The encoded protein contains a gyf protein interaction domain. It binds growth factor receptor bound 10, another adaptor protein that binds activated insulin-like growth factor 1 and insulin receptors and regulates receptor signaling. [provided by RefSeq, Apr 2017]

GIGYF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 7-100682365-G-A is Benign according to our data. Variant chr7-100682365-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038257.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF1	NM_001375765.1 link	c.2718C>T	p.Cys906Cys	synonymous_variant	Exon 24 of 27	ENST00000678049.1	NP_001362694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GIGYF1	ENST00000678049.1 link	c.2718C>T	p.Cys906Cys	synonymous_variant	Exon 24 of 27		NM_001375765.1	ENSP00000503354.1	O75420
GIGYF1	ENST00000275732.5 link	c.2718C>T	p.Cys906Cys	synonymous_variant	Exon 21 of 24	1		ENSP00000275732.4	O75420
GIGYF1	ENST00000646601.1 link	c.2718C>T	p.Cys906Cys	synonymous_variant	Exon 25 of 28			ENSP00000494292.1	O75420

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

281

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00148

AC:

365

AN:

246496

Hom.:

AF XY:

0.00148

AC XY:

198

AN XY:

133380

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000233

Gnomad NFE exome

AF:

0.00265

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00222

AC:

3242

AN:

1461132

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

1563

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000360

Gnomad4 NFE exome

AF:

0.00271

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00184

AC:

281

AN:

152332

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00262

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00233

Hom.:

Bravo

AF:

0.00193

EpiCase

AF:

0.00305

EpiControl

AF:

0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GIGYF1-related disorder

Benign:1

May 02, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.72

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.72

Position offset: 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