7-1091720-T-C

Variant names:

• chr7-1091720-T-C
• rs3802141
• NM_001098201.3:c.-9T>C

Variant summary

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

The NM_001098201.3(GPER1):​c.-9T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 1,514,496 control chromosomes in the GnomAD database, including 298,678 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 0.67 (34416 hom., cov: 34)
  • Exomes 𝑓: 0.62 (264262 hom.)
• Consequence: GPER1 NM_001098201.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.-9T>C		5_prime_UTR_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1
CHLSN	NM_001318252.2	c.129+35537A>G		intron_variant	Intron 2 of 4	ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4	c.-9T>C		5_prime_UTR_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+35537A>G		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101140 AN: 152036 Hom.: 34376 Cov.: 34

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.640

GnomAD2 exomes AF: 0.620 AC: 113415 AN: 182798 AF XY: 0.615

Gnomad AFR exome AF: 0.801

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.629

Gnomad EAS exome AF: 0.409

Gnomad FIN exome AF: 0.645

Gnomad NFE exome AF: 0.616

Gnomad OTH exome AF: 0.615

GnomAD4 exome AF: 0.620 AC: 845122 AN: 1362342 Hom.: 264262 Cov.: 31 AF XY: 0.619 AC XY: 413524 AN XY: 667922

African (AFR) AF: 0.808 AC: 24508 AN: 30328

American (AMR) AF: 0.658 AC: 20103 AN: 30546

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 12622 AN: 20182

East Asian (EAS) AF: 0.504 AC: 19572 AN: 38818

South Asian (SAS) AF: 0.598 AC: 42479 AN: 70998

European-Finnish (FIN) AF: 0.643 AC: 31730 AN: 49362

Middle Eastern (MID) AF: 0.620 AC: 3281 AN: 5296

European-Non Finnish (NFE) AF: 0.619 AC: 656364 AN: 1060652

Other (OTH) AF: 0.614 AC: 34463 AN: 56160

GnomAD4 genome AF: 0.665 AC: 101225 AN: 152154 Hom.: 34416 Cov.: 34 AF XY: 0.662 AC XY: 49214 AN XY: 74358

African (AFR) AF: 0.797 AC: 33090 AN: 41542

American (AMR) AF: 0.635 AC: 9709 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2178 AN: 5148

South Asian (SAS) AF: 0.581 AC: 2803 AN: 4824

European-Finnish (FIN) AF: 0.640 AC: 6756 AN: 10564

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42385 AN: 67992

Other (OTH) AF: 0.636 AC: 1345 AN: 2114

Alfa AF: 0.632 Hom.: 53970

Bravo AF: 0.669

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.037
DANN	Benign	0.31
PhyloP100		-2.7
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)		0.0		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: rs3802141; hg19: chr7-1131356; COSMIC: COSV52467847; COSMIC: COSV52467847;