7-1082213-A-G

Position:

• chr7-1082213-A-G

Variant summary

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

The NM_001318252.2(C7orf50):​c.129+45044T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,260 control chromosomes in the GnomAD database, including 38,391 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 0.70 (38381 hom., cov: 34)
  • Exomes 𝑓: 0.67 (10 hom.)
• Consequence: C7orf50 NM_001318252.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

Genes affected

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C7orf50	NM_001318252.2	c.129+45044T>C		intron_variant		ENST00000397098.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C7orf50	ENST00000397098.8	c.129+45044T>C		intron_variant		1	NM_001318252.2	P1
	ENST00000415656.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.697 AC: 106074 AN: 152106 Hom.: 38321 Cov.: 34

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.667 AC: 24 AN: 36 Hom.: 10 Cov.: 0 AF XY: 0.750 AC XY: 15 AN XY: 20

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.698 AC: 106185 AN: 152224 Hom.: 38381 Cov.: 34 AF XY: 0.692 AC XY: 51530 AN XY: 74416

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.655

Alfa AF: 0.691 Hom.: 4625

Bravo AF: 0.704

Asia WGS AF: 0.521 AC: 1812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12701969; hg19: chr7-1121849;