rs696851

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR149	NM_001038705.3	c.1623+35517C>T		intron_variant		ENST00000389740.3	NP_001033794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR149	ENST00000389740.3	c.1623+35517C>T		intron_variant		1	NM_001038705.3	ENSP00000374390	P1

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

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.776

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.55

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: rs696851; hg19: chr3-154103311;