NM_001318252.2:c.129+41000T>C

Variant names:

• chr7-1086257-A-G
• rs3808350
• NM_001318252.2:c.129+41000T>C

Variant summary

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

The NM_001318252.2(CHLSN):​c.129+41000T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,110 control chromosomes in the GnomAD database, including 19,191 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 0.48 (19191 hom., cov: 33)
• Consequence: CHLSN NM_001318252.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 20 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318252.2. 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+41000T>C		intron	N/A	NP_001305181.1
	CHLSN	NM_001424325.1		c.129+41000T>C		intron	N/A	NP_001411254.1
	CHLSN	NM_001424326.1		c.129+41000T>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+41000T>C		intron	N/A	ENSP00000380286.3
	C7orf50	ENST00000357429.10	TSL:1	c.129+41000T>C		intron	N/A	ENSP00000350011.5
	GPER1	ENST00000401670.1	TSL:2	c.-323+3983A>G		intron	N/A	ENSP00000385151.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72596 AN: 151992 Hom.: 19164 Cov.: 33

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.435

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.478 AC: 72673 AN: 152110 Hom.: 19191 Cov.: 33 AF XY: 0.474 AC XY: 35216 AN XY: 74362

African (AFR) AF: 0.715 AC: 29669 AN: 41482

American (AMR) AF: 0.404 AC: 6176 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2100 AN: 5174

South Asian (SAS) AF: 0.347 AC: 1671 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4549 AN: 10560

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26129 AN: 68000

Other (OTH) AF: 0.433 AC: 915 AN: 2114

Alfa AF: 0.395 Hom.: 19436

Bravo AF: 0.486

Asia WGS AF: 0.414 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.72
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3808350; hg19: chr7-1125893;