chr7-1093669-C-G

Position:

• chr7-1093669-C-G

Variant summary

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

The NM_001098201.3(GPER1):​c.*813C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 469,890 control chromosomes in the GnomAD database, including 93,478 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 0.65 (32780 hom., cov: 34)
  • Exomes 𝑓: 0.61 (60698 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=1.6484207E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*813C>G		3_prime_UTR_variant	2/2	ENST00000397088.4	NP_001091671.1
C7orf50	NM_001318252.2	c.129+33588G>C		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4	c.*813C>G		3_prime_UTR_variant	2/2	1	NM_001098201.3	ENSP00000380277	P1
C7orf50	ENST00000397098.8	c.129+33588G>C		intron_variant		1	NM_001318252.2	ENSP00000380286	P1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98932 AN: 152076 Hom.: 32745 Cov.: 34

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.625

GnomAD3 exomes AF: 0.607 AC: 92084 AN: 151652 Hom.: 28474 AF XY: 0.604 AC XY: 49144 AN XY: 81310

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.627

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.381

Gnomad SAS exome AF: 0.576

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.599

GnomAD4 exome AF: 0.615 AC: 195369 AN: 317696 Hom.: 60698 Cov.: 0 AF XY: 0.611 AC XY: 109509 AN XY: 179260

Gnomad4 AFR exome AF: 0.752

Gnomad4 AMR exome AF: 0.629

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.409

Gnomad4 SAS exome AF: 0.580

Gnomad4 FIN exome AF: 0.645

Gnomad4 NFE exome AF: 0.624

Gnomad4 OTH exome AF: 0.614

GnomAD4 genome AF: 0.651 AC: 99009 AN: 152194 Hom.: 32780 Cov.: 34 AF XY: 0.647 AC XY: 48124 AN XY: 74404

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.622

Alfa AF: 0.588 Hom.: 3343

Bravo AF: 0.651

TwinsUK AF: 0.616 AC: 2283

ALSPAC AF: 0.619 AC: 2385

ExAC AF: 0.583 AC: 12060

Asia WGS AF: 0.508 AC: 1765 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.43
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
Vest4		0.057
ClinPred		0.0043	T
GERP RS		-0.41

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: rs1133043; hg19: chr7-1133305;