rs117290655

Variant names:

• chr7-1091742-C-T
• rs117290655
• NM_001098201.3:c.14C>T

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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
• Publications: 6 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098201.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPER1	NM_001098201.3	MANE Select	c.14C>T	p.Ser5Phe	missense	Exon 2 of 2	NP_001091671.1	Q99527
	CHLSN	NM_001318252.2	MANE Select	c.129+35515G>A		intron	N/A	NP_001305181.1	Q9BRJ6
	GPER1	NM_001039966.2		c.14C>T	p.Ser5Phe	missense	Exon 3 of 3	NP_001035055.1	Q99527

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPER1	ENST00000397088.4	TSL:1 MANE Select	c.14C>T	p.Ser5Phe	missense	Exon 2 of 2	ENSP00000380277.3	Q99527
	GPER1	ENST00000297469.3	TSL:1	c.14C>T	p.Ser5Phe	missense	Exon 2 of 2	ENSP00000297469.3	Q99527
	CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.129+35515G>A		intron	N/A	ENSP00000380286.3	Q9BRJ6

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

GnomAD2 exomes AF: 0.00915 AC: 1745 AN: 190654 AF XY: 0.00791

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 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

African (AFR) AF: 0.00126 AC: 39 AN: 30860

American (AMR) AF: 0.0320 AC: 1046 AN: 32730

Ashkenazi Jewish (ASJ) AF: 0.000914 AC: 19 AN: 20784

East Asian (EAS) AF: 0.0254 AC: 990 AN: 38918

South Asian (SAS) AF: 0.000633 AC: 46 AN: 72662

European-Finnish (FIN) AF: 0.00229 AC: 114 AN: 49790

Middle Eastern (MID) AF: 0.000374 AC: 2 AN: 5354

European-Non Finnish (NFE) AF: 0.00474 AC: 5076 AN: 1070716

Other (OTH) AF: 0.00548 AC: 311 AN: 56710

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

African (AFR) AF: 0.00151 AC: 63 AN: 41594

American (AMR) AF: 0.0114 AC: 175 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.0242 AC: 125 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00103 AC: 11 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00573 AC: 390 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00651 Hom.: 4

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.077
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.15	T
Polyphen		0.0	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
Mutation Taster		=100/0	polymorphism

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