1-202123452-T-C

Position:

• chr1-202123452-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004767.5(GPR37L1):​c.489T>C​(p.Ser163=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 1,613,850 control chromosomes in the GnomAD database, including 642,835 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 0.85 (55957 hom., cov: 31)
  • Exomes 𝑓: 0.90 (586878 hom.)
• Consequence: GPR37L1 NM_004767.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76

Genes affected

GPR37L1 (HGNC:14923): (G protein-coupled receptor 37 like 1) Enables G protein-coupled peptide receptor activity; peptide binding activity; and prosaposin receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and positive regulation of MAPK cascade. Located in plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-2.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR37L1	NM_004767.5	c.489T>C	p.Ser163=	synonymous_variant	1/2	ENST00000367282.6	NP_004758.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR37L1	ENST00000367282.6	c.489T>C	p.Ser163=	synonymous_variant	1/2	1	NM_004767.5	ENSP00000356251	P1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129855 AN: 151922 Hom.: 55923 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.853

GnomAD3 exomes AF: 0.880 AC: 221086 AN: 251128 Hom.: 97682 AF XY: 0.887 AC XY: 120339 AN XY: 135716

Gnomad AFR exome AF: 0.740

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.856

Gnomad EAS exome AF: 0.829

Gnomad SAS exome AF: 0.918

Gnomad FIN exome AF: 0.952

Gnomad NFE exome AF: 0.903

Gnomad OTH exome AF: 0.890

GnomAD4 exome AF: 0.895 AC: 1308627 AN: 1461810 Hom.: 586878 Cov.: 63 AF XY: 0.896 AC XY: 651817 AN XY: 727204

Gnomad4 AFR exome AF: 0.733

Gnomad4 AMR exome AF: 0.831

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.806

Gnomad4 SAS exome AF: 0.920

Gnomad4 FIN exome AF: 0.950

Gnomad4 NFE exome AF: 0.903

Gnomad4 OTH exome AF: 0.885

GnomAD4 genome AF: 0.855 AC: 129934 AN: 152040 Hom.: 55957 Cov.: 31 AF XY: 0.856 AC XY: 63604 AN XY: 74306

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.853

Alfa AF: 0.877 Hom.: 42470

Bravo AF: 0.839

Asia WGS AF: 0.865 AC: 3009 AN: 3478

EpiCase AF: 0.893

EpiControl AF: 0.895

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.52

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: rs7516762; hg19: chr1-202092580;