7-100682365-G-A

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

2

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]

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/exons MANE Protein UniProt
GIGYF1NM_001375765.1 linkuse as main transcriptc.2718C>T p.Cys906Cys synonymous_variant 24/27 ENST00000678049.1 NP_001362694.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GIGYF1ENST00000678049.1 linkuse as main transcriptc.2718C>T p.Cys906Cys synonymous_variant 24/27 NM_001375765.1 ENSP00000503354.1 O75420
GIGYF1ENST00000275732.5 linkuse as main transcriptc.2718C>T p.Cys906Cys synonymous_variant 21/241 ENSP00000275732.4 O75420
GIGYF1ENST00000646601.1 linkuse as main transcriptc.2718C>T p.Cys906Cys synonymous_variant 25/28 ENSP00000494292.1 O75420

Frequencies

GnomAD3 genomes
AF:
0.00185
AC:
281
AN:
152214
Hom.:
1
Cov.:
33
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.:
1
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.:
3
Cov.:
33
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.:
1
Cov.:
33
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.:
0
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
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMay 02, 2019This 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
18
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.

Other links and lift over

dbSNP: rs117477530; hg19: chr7-100279988; API