rs10235056

Positions:

• chr7-1093112-G-A

Variant summary

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

The NM_001098201.3(GPER1):​c.*256G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 652,682 control chromosomes in the GnomAD database, including 2,447 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 0.081 (551 hom., cov: 33)
  • Exomes 𝑓: 0.081 (1896 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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=0.0016965866).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*256G>A		3_prime_UTR_variant	2/2	ENST00000397088.4	NP_001091671.1
C7orf50	NM_001318252.2	c.129+34145C>T		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4	c.*256G>A		3_prime_UTR_variant	2/2	1	NM_001098201.3	ENSP00000380277	P1
C7orf50	ENST00000397098.8	c.129+34145C>T		intron_variant		1	NM_001318252.2	ENSP00000380286	P1

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12321 AN: 152020 Hom.: 549 Cov.: 33

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.0664

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0898

Gnomad OTH AF: 0.0794

GnomAD3 exomes AF: 0.0822 AC: 12068 AN: 146790 Hom.: 617 AF XY: 0.0811 AC XY: 6427 AN XY: 79242

Gnomad AFR exome AF: 0.0713

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.0740

Gnomad EAS exome AF: 0.0222

Gnomad SAS exome AF: 0.0688

Gnomad FIN exome AF: 0.0602

Gnomad NFE exome AF: 0.0899

Gnomad OTH exome AF: 0.0813

GnomAD4 exome AF: 0.0808 AC: 40461 AN: 500544 Hom.: 1896 Cov.: 0 AF XY: 0.0803 AC XY: 21816 AN XY: 271644

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.0715

Gnomad4 EAS exome AF: 0.0207

Gnomad4 SAS exome AF: 0.0702

Gnomad4 FIN exome AF: 0.0592

Gnomad4 NFE exome AF: 0.0880

Gnomad4 OTH exome AF: 0.0822

GnomAD4 genome AF: 0.0811 AC: 12333 AN: 152138 Hom.: 551 Cov.: 33 AF XY: 0.0794 AC XY: 5907 AN XY: 74372

Gnomad4 AFR AF: 0.0704

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.0899

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0911 Hom.: 270

Bravo AF: 0.0844

TwinsUK AF: 0.0965 AC: 358

ALSPAC AF: 0.0833 AC: 321

ExAC AF: 0.0509 AC: 1487

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.34
DANN	Benign	0.49
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
Sift4G	Pathogenic	0.0	D;D
Vest4		0.086
ClinPred		0.0018	T
GERP RS		-2.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.3

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: rs10235056; hg19: chr7-1132748;