7-1088069-G-T

Variant names:

• chr7-1088069-G-T
• rs33987461
• NM_001318252.2:c.129+39188C>A

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+39188C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 152,268 control chromosomes in the GnomAD database, including 66 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 0.017 (66 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHLSN NM_001318252.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHLSN	NM_001318252.2	MANE Select	c.129+39188C>A		intron	N/A	NP_001305181.1	Q9BRJ6
	GPER1	NM_001039966.2		c.-446-129G>T		intron	N/A	NP_001035055.1	Q99527
	GPER1	NM_001505.3		c.-323+825G>T		intron	N/A	NP_001496.1	Q99527

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.129+39188C>A		intron	N/A	ENSP00000380286.3	Q9BRJ6
	GPER1	ENST00000297469.3	TSL:1	c.-323+825G>T		intron	N/A	ENSP00000297469.3	Q99527
	CHLSN	ENST00000357429.10	TSL:1	c.129+39188C>A		intron	N/A	ENSP00000350011.5	Q9BRJ6

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2557 AN: 152150 Hom.: 66 Cov.: 33

Gnomad AFR AF: 0.00343

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0153

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 84 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 62

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 72

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0168 AC: 2553 AN: 152268 Hom.: 66 Cov.: 33 AF XY: 0.0186 AC XY: 1387 AN XY: 74452

African (AFR) AF: 0.00342 AC: 142 AN: 41566

American (AMR) AF: 0.00693 AC: 106 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3466

East Asian (EAS) AF: 0.133 AC: 690 AN: 5178

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4814

European-Finnish (FIN) AF: 0.0434 AC: 461 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0142 AC: 967 AN: 68006

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.00504 Hom.: 2

Bravo AF: 0.0154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		0.12
PromoterAI		0.047	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs33987461; hg19: chr7-1127705;