7-1082213-A-G

Variant names:

• chr7-1082213-A-G
• rs12701969
• NM_001318252.2:c.129+45044T>C

Variant summary

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

The ENST00000397098.8(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 ENST00000397098.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 3 publications found

Genes affected

CHLSN (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]

ENSG00000226291 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397098.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHLSN	NM_001318252.2	MANE Select	c.129+45044T>C		intron	N/A	NP_001305181.1
	CHLSN	NM_001424325.1		c.129+45044T>C		intron	N/A	NP_001411254.1
	CHLSN	NM_001424326.1		c.129+45044T>C		intron	N/A	NP_001411255.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7orf50	ENST00000397098.8	TSL:1 MANE Select	c.129+45044T>C		intron	N/A	ENSP00000380286.3
	C7orf50	ENST00000357429.10	TSL:1	c.129+45044T>C		intron	N/A	ENSP00000350011.5
	GPER1	ENST00000401670.1	TSL:2	c.-384A>G		5_prime_UTR	Exon 1 of 2	ENSP00000385151.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 8 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.682 AC: 15 AN: 22

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.889 AC: 36920 AN: 41548

American (AMR) AF: 0.637 AC: 9749 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2086 AN: 3468

East Asian (EAS) AF: 0.416 AC: 2150 AN: 5166

South Asian (SAS) AF: 0.551 AC: 2658 AN: 4824

European-Finnish (FIN) AF: 0.648 AC: 6875 AN: 10606

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43579 AN: 67998

Other (OTH) AF: 0.655 AC: 1384 AN: 2112

Alfa AF: 0.699 Hom.: 4925

Bravo AF: 0.704

Asia WGS AF: 0.521 AC: 1812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		0.039
PromoterAI		-0.0064	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12701969; hg19: chr7-1121849;