chr7-1093035-C-G

Position:

• chr7-1093035-C-G

Variant summary

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

The NM_001098201.3(GPER1):​c.*179C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 720,544 control chromosomes in the GnomAD database, including 4,595 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 0.11 (923 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3672 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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 (MetaRNN=0.0017130375).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*179C>G		3_prime_UTR_variant	2/2	ENST00000397088.4	NP_001091671.1
C7orf50	NM_001318252.2	c.129+34222G>C		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4	c.*179C>G		3_prime_UTR_variant	2/2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+34222G>C		intron_variant		1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15990 AN: 152042 Hom.: 921 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.106 AC: 15928 AN: 149792 Hom.: 958 AF XY: 0.109 AC XY: 8823 AN XY: 80648

Gnomad AFR exome AF: 0.0963

Gnomad AMR exome AF: 0.0879

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0439

Gnomad SAS exome AF: 0.132

Gnomad FIN exome AF: 0.0868

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.109 AC: 61745 AN: 568386 Hom.: 3672 Cov.: 5 AF XY: 0.110 AC XY: 33805 AN XY: 306454

Gnomad4 AFR exome AF: 0.0986

Gnomad4 AMR exome AF: 0.0895

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0401

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0839

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.105 AC: 15995 AN: 152158 Hom.: 923 Cov.: 32 AF XY: 0.103 AC XY: 7634 AN XY: 74378

Gnomad4 AFR AF: 0.0976

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0808

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0907 Hom.: 280

Bravo AF: 0.104

TwinsUK AF: 0.121 AC: 448

ALSPAC AF: 0.127 AC: 488

ExAC AF: 0.0632 AC: 2876

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.55
DANN	Benign	0.60
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.32	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.0	T
Sift4G	Pathogenic	0.0	D;D
Vest4		0.12
ClinPred		0.0026	T
GERP RS		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs4266553; hg19: chr7-1132671;