rs10269151

Variant names:

• chr7-1087240-G-A
• rs10269151
• ENST00000297469.3:c.-327G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000297469.3(GPER1):​c.-327G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,292 control chromosomes in the GnomAD database, including 212 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 0.046 (212 hom., cov: 33)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: GPER1 ENST00000297469.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 11 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 (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000297469.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHLSN	NM_001318252.2	MANE Select	c.129+40017C>T		intron	N/A	NP_001305181.1
	GPER1	NM_001039966.2		c.-451G>A		5_prime_UTR	Exon 1 of 3	NP_001035055.1
	GPER1	NM_001505.3		c.-327G>A		5_prime_UTR	Exon 1 of 2	NP_001496.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPER1	ENST00000297469.3	TSL:1	c.-327G>A		5_prime_UTR	Exon 1 of 2	ENSP00000297469.3
	C7orf50	ENST00000397098.8	TSL:1 MANE Select	c.129+40017C>T		intron	N/A	ENSP00000380286.3
	C7orf50	ENST00000357429.10	TSL:1	c.129+40017C>T		intron	N/A	ENSP00000350011.5

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6928 AN: 152164 Hom.: 212 Cov.: 33

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0304

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0455 AC: 6930 AN: 152280 Hom.: 212 Cov.: 33 AF XY: 0.0460 AC XY: 3425 AN XY: 74454

African (AFR) AF: 0.0665 AC: 2762 AN: 41556

American (AMR) AF: 0.0455 AC: 696 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.0676 AC: 350 AN: 5180

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4824

European-Finnish (FIN) AF: 0.0783 AC: 831 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0304 AC: 2068 AN: 68024

Other (OTH) AF: 0.0398 AC: 84 AN: 2110

Alfa AF: 0.0328 Hom.: 138

Bravo AF: 0.0443

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		-0.44
PromoterAI		-0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10269151; hg19: chr7-1126876;