7-100679371-A-G

Variant names:

• chr7-100679371-A-G
• rs11520986
• NM_001375765.1:c.*2348T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784

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]

ACMG classification

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
GIGYF1	NM_001375765.1	c.*2348T>C		downstream_gene_variant		ENST00000678049.1	NP_001362694.1
GNB2	NM_005273.4	c.*570A>G		downstream_gene_variant		ENST00000303210.9	NP_005264.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF1	ENST00000678049.1	c.*2348T>C		downstream_gene_variant			NM_001375765.1	ENSP00000503354.1
GNB2	ENST00000303210.9	c.*570A>G		downstream_gene_variant		1	NM_005273.4	ENSP00000305260.4

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34114 AN: 151914 Hom.: 3882 Cov.: 32

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

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

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

Other links and lift over

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