7-1093535-G-T

Position:

• chr7-1093535-G-T

Variant summary

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

The NM_001098201.3(GPER1):​c.*679G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 470,740 control chromosomes in the GnomAD database, including 8,508 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 0.21 (4318 hom., cov: 33)
  • Exomes 𝑓: 0.15 (4190 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

Genes affected

GPER1 (HGNC:4485): (G protein-coupled estrogen receptor 1) This gene encodes a multi-pass membrane protein that localizes to the endoplasmic reticulum and a member of the G-protein coupled receptor 1 family. This receptor binds estrogen and activates multiple downstream signaling pathways, leading to stimulation of adenylate cyclase and an increase in cyclic AMP levels, while also promoting intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. This receptor has been shown to play a role in diverse biological processes, including bone and nervous system development, metabolism, cognition, male fertility and uterine function. [provided by RefSeq, Aug 2017]

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024252534).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*679G>T		3_prime_UTR_variant	2/2	ENST00000397088.4	NP_001091671.1
C7orf50	NM_001318252.2	c.129+33722C>A		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4	c.*679G>T		3_prime_UTR_variant	2/2	1	NM_001098201.3	ENSP00000380277	P1
C7orf50	ENST00000397098.8	c.129+33722C>A		intron_variant		1	NM_001318252.2	ENSP00000380286	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32088 AN: 151998 Hom.: 4309 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0780

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.205

GnomAD3 exomes AF: 0.149 AC: 22478 AN: 151050 Hom.: 2007 AF XY: 0.149 AC XY: 12118 AN XY: 81200

Gnomad AFR exome AF: 0.395

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.0677

Gnomad SAS exome AF: 0.157

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.152 AC: 48315 AN: 318624 Hom.: 4190 Cov.: 0 AF XY: 0.153 AC XY: 27522 AN XY: 180000

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.0686

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.211 AC: 32129 AN: 152116 Hom.: 4318 Cov.: 33 AF XY: 0.206 AC XY: 15359 AN XY: 74380

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0778

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.206

Alfa AF: 0.151 Hom.: 1553

Bravo AF: 0.220

TwinsUK AF: 0.149 AC: 552

ALSPAC AF: 0.160 AC: 617

ExAC AF: 0.146 AC: 2886

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.58
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
Vest4		0.13
ClinPred		0.0033	T
GERP RS		-3.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs3808354; hg19: chr7-1133171; COSMIC: COSV52467725; COSMIC: COSV52467725;