chr7-1087240-G-A

Position:

• chr7-1087240-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7orf50	NM_001318252.2	c.129+40017C>T		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7orf50	ENST00000397098.8	c.129+40017C>T		intron_variant		1	NM_001318252.2	ENSP00000380286	P1

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

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

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

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.0676

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.0783

Gnomad4 NFE AF: 0.0304

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0313 Hom.: 93

Bravo AF: 0.0443

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs10269151; hg19: chr7-1126876;