rs696851

Variant names:

• chr3-154385522-G-A
• rs696851
• NM_001038705.3:c.1623+35517C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-154385522-G-A
• chr3-154385522-G-C
• chr3-154385522-G-T

Variant summary

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

The NM_001038705.3(GPR149):​c.1623+35517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 151,988 control chromosomes in the GnomAD database, including 46,223 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 0.77 (46223 hom., cov: 30)
• Consequence: GPR149 NM_001038705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 1 publications found

Genes affected

GPR149 (HGNC:23627): (G protein-coupled receptor 149) This gene encodes a seven-transmembrane G protein coupled receptor (GPCR) class A family member. Although categorized as a class A GPCR, the encoded protein lacks the first two charged amino acids of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix of class A receptors which is important for efficient G protein-coupled signal transduction. Mice with a knockout of the orthologous gene are viable and have normal maturation of the ovarian follicle, but show enhanced fertility and ovulation. All GPCRs have a common structural architecture consisting of seven transmembrane alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptor, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. [provided by RefSeq, Jul 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001038705.3. 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
	GPR149	NM_001038705.3	MANE Select	c.1623+35517C>T		intron	N/A	NP_001033794.1	Q86SP6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR149	ENST00000389740.3	TSL:1 MANE Select	c.1623+35517C>T		intron	N/A	ENSP00000374390.2	Q86SP6

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117290 AN: 151872 Hom.: 46226 Cov.: 30

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.917

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.772 AC: 117325 AN: 151988 Hom.: 46223 Cov.: 30 AF XY: 0.773 AC XY: 57416 AN XY: 74288

African (AFR) AF: 0.600 AC: 24831 AN: 41402

American (AMR) AF: 0.776 AC: 11849 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2967 AN: 3470

East Asian (EAS) AF: 0.754 AC: 3870 AN: 5136

South Asian (SAS) AF: 0.862 AC: 4148 AN: 4810

European-Finnish (FIN) AF: 0.830 AC: 8789 AN: 10590

Middle Eastern (MID) AF: 0.911 AC: 266 AN: 292

European-Non Finnish (NFE) AF: 0.855 AC: 58139 AN: 67990

Other (OTH) AF: 0.776 AC: 1641 AN: 2114

Alfa AF: 0.816 Hom.: 8675

Bravo AF: 0.757

Asia WGS AF: 0.761 AC: 2646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.55
PhyloP100		0.050
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: rs696851; hg19: chr3-154103311;