rs3808351

Positions:

• chr7-1087023-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000297469(GPER1):​c.-544G>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 0.288 in 152,238 control chromosomes in the GnomAD database, including 6,572 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 0.29 (6570 hom., cov: 33)
  • Exomes 𝑓: 0.41 (2 hom.)
• Consequence: GPER1 ENST00000297469 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7orf50	NM_001318252.2	c.129+40234C>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+40234C>T		intron_variant		1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43862 AN: 152098 Hom.: 6557 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.409 AC: 9 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.417 AC XY: 5 AN XY: 12

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.450

GnomAD4 genome AF: 0.288 AC: 43901 AN: 152216 Hom.: 6570 Cov.: 33 AF XY: 0.286 AC XY: 21254 AN XY: 74426

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.286

Alfa AF: 0.297 Hom.: 5965

Bravo AF: 0.284

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.72

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: rs3808351; hg19: chr7-1126659;