chr7-1093535-G-T

Variant names:

• chr7-1093535-G-T
• rs3808354
• NM_001098201.3:c.*679G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*679G>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1
CHLSN	NM_001318252.2	c.129+33722C>A		intron_variant	Intron 2 of 4	ENST00000397098.8	NP_001305181.1

Ensembl

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

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

GnomAD2 exomes AF: 0.149 AC: 22478 AN: 151050 AF XY: 0.149

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 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

African (AFR) AF: 0.393 AC: 3393 AN: 8632

American (AMR) AF: 0.119 AC: 3259 AN: 27286

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 1842 AN: 10790

East Asian (EAS) AF: 0.0686 AC: 632 AN: 9214

South Asian (SAS) AF: 0.156 AC: 9326 AN: 59742

European-Finnish (FIN) AF: 0.116 AC: 3109 AN: 26834

Middle Eastern (MID) AF: 0.118 AC: 328 AN: 2776

European-Non Finnish (NFE) AF: 0.151 AC: 24068 AN: 159028

Other (OTH) AF: 0.165 AC: 2358 AN: 14322

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

African (AFR) AF: 0.385 AC: 15949 AN: 41474

American (AMR) AF: 0.157 AC: 2402 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3464

East Asian (EAS) AF: 0.0778 AC: 402 AN: 5166

South Asian (SAS) AF: 0.148 AC: 712 AN: 4822

European-Finnish (FIN) AF: 0.113 AC: 1192 AN: 10594

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10244 AN: 68000

Other (OTH) AF: 0.206 AC: 436 AN: 2116

Alfa AF: 0.152 Hom.: 1661

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
PhyloP100		-2.1
Vest4		0.13
ClinPred		0.0033	T
GERP RS		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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