7-1091742-C-T

Position:

• chr7-1091742-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001098201.3(GPER1):​c.14C>T​(p.Ser5Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,530,888 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (6 hom., cov: 34)
  • Exomes 𝑓: 0.0055 (61 hom.)
• Consequence: GPER1 NM_001098201.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0770

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]

C7orf50 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030380487).
• BP6: Variant 7-1091742-C-T is Benign according to our data. Variant chr7-1091742-C-T is described in ClinVar as [Benign]. Clinvar id is 770179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0051 (777/152364) while in subpopulation EAS AF= 0.0242 (125/5174). AF 95% confidence interval is 0.0207. There are 6 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.14C>T	p.Ser5Phe	missense_variant	2/2	ENST00000397088.4	NP_001091671.1
C7orf50	NM_001318252.2	c.129+35515G>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.14C>T	p.Ser5Phe	missense_variant	2/2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+35515G>A		intron_variant		1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.00511 AC: 778 AN: 152246 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00573

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00915 AC: 1745 AN: 190654 Hom.: 33 AF XY: 0.00791 AC XY: 797 AN XY: 100772

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.0360

Gnomad ASJ exome AF: 0.000454

Gnomad EAS exome AF: 0.0234

Gnomad SAS exome AF: 0.000772

Gnomad FIN exome AF: 0.00169

Gnomad NFE exome AF: 0.00440

Gnomad OTH exome AF: 0.00612

GnomAD4 exome AF: 0.00554 AC: 7643 AN: 1378524 Hom.: 61 Cov.: 34 AF XY: 0.00540 AC XY: 3654 AN XY: 676238

Gnomad4 AFR exome AF: 0.00126

Gnomad4 AMR exome AF: 0.0320

Gnomad4 ASJ exome AF: 0.000914

Gnomad4 EAS exome AF: 0.0254

Gnomad4 SAS exome AF: 0.000633

Gnomad4 FIN exome AF: 0.00229

Gnomad4 NFE exome AF: 0.00474

Gnomad4 OTH exome AF: 0.00548

GnomAD4 genome AF: 0.00510 AC: 777 AN: 152364 Hom.: 6 Cov.: 34 AF XY: 0.00525 AC XY: 391 AN XY: 74502

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0242

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00103

Gnomad4 NFE AF: 0.00573

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00508 Hom.: 3

Bravo AF: 0.00694

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00477 AC: 41

ExAC AF: 0.00823 AC: 994

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.6
DANN	Uncertain	0.97
DEOGEN2	Benign	0.055	T;T;T;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.57	.;T;T;.;.;T
MetaRNN	Benign	0.0030	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;.;N;N;N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.24	N;D;N;N;N;.
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D;D;D;D;D;.
Sift4G	Benign	0.15	T;D;T;T;T;D
Polyphen		0.0	B;.;B;B;B;.
Vest4		0.047
MVP		0.10
MPC		0.45
ClinPred		0.0029	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.53

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: rs117290655; hg19: chr7-1131378; COSMIC: COSV52469765; COSMIC: COSV52469765;