7-100679371-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001375765.1(GIGYF1):​c.*2348T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 153,182 control chromosomes in the GnomAD database, including 3,927 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3888 hom., cov: 32)
Exomes 𝑓: 0.21 ( 39 hom. )

Consequence

GIGYF1
NM_001375765.1 downstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.784
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]
GNB2 (HGNC:4398): (G protein subunit beta 2) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. This gene contains a trinucleotide (CCG) repeat length polymorphism in its 5' UTR. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GIGYF1NM_001375765.1 linkc.*2348T>C downstream_gene_variant ENST00000678049.1 NP_001362694.1
GNB2NM_005273.4 linkc.*570A>G downstream_gene_variant ENST00000303210.9 NP_005264.2 P62879-1Q6FHM2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GIGYF1ENST00000678049.1 linkc.*2348T>C downstream_gene_variant NM_001375765.1 ENSP00000503354.1 O75420
GNB2ENST00000303210.9 linkc.*570A>G downstream_gene_variant 1 NM_005273.4 ENSP00000305260.4 P62879-1

Frequencies

GnomAD3 genomes
AF:
0.225
AC:
34114
AN:
151914
Hom.:
3882
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.222
Gnomad AMI
AF:
0.302
Gnomad AMR
AF:
0.182
Gnomad ASJ
AF:
0.197
Gnomad EAS
AF:
0.123
Gnomad SAS
AF:
0.135
Gnomad FIN
AF:
0.265
Gnomad MID
AF:
0.0949
Gnomad NFE
AF:
0.246
Gnomad OTH
AF:
0.190
GnomAD4 exome
AF:
0.211
AC:
243
AN:
1150
Hom.:
39
AF XY:
0.214
AC XY:
137
AN XY:
640
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.160
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0769
Gnomad4 FIN exome
AF:
0.279
Gnomad4 NFE exome
AF:
0.223
Gnomad4 OTH exome
AF:
0.176
GnomAD4 genome
AF:
0.225
AC:
34153
AN:
152032
Hom.:
3888
Cov.:
32
AF XY:
0.219
AC XY:
16291
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.222
Gnomad4 AMR
AF:
0.181
Gnomad4 ASJ
AF:
0.197
Gnomad4 EAS
AF:
0.123
Gnomad4 SAS
AF:
0.137
Gnomad4 FIN
AF:
0.265
Gnomad4 NFE
AF:
0.246
Gnomad4 OTH
AF:
0.188
Alfa
AF:
0.232
Hom.:
4045
Bravo
AF:
0.221
Asia WGS
AF:
0.152
AC:
527
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.54
DANN
Benign
0.41

Splicing

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: rs11520986; hg19: chr7-100276994; COSMIC: COSV51947190; API