rs7516762

Variant names:

• chr1-202123452-T-C
• rs7516762
• NM_004767.5:c.489T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-202123452-T-C
• chr1-202123452-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004767.5(GPR37L1):​c.489T>C​(p.Ser163Ser) 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
• Publications: 18 publications found

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]

ENSG00000294430 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004767.5. 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
	GPR37L1	NM_004767.5	MANE Select	c.489T>C	p.Ser163Ser	synonymous	Exon 1 of 2	NP_004758.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR37L1	ENST00000367282.6	TSL:1 MANE Select	c.489T>C	p.Ser163Ser	synonymous	Exon 1 of 2	ENSP00000356251.4
	GPR37L1	ENST00000683302.1		c.489T>C	p.Ser163Ser	synonymous	Exon 1 of 3	ENSP00000507885.1
	GPR37L1	ENST00000683557.1		c.489T>C	p.Ser163Ser	synonymous	Exon 1 of 3	ENSP00000508029.1

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

GnomAD2 exomes AF: 0.880 AC: 221086 AN: 251128 AF XY: 0.887

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 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

African (AFR) AF: 0.733 AC: 24535 AN: 33476

American (AMR) AF: 0.831 AC: 37148 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 22408 AN: 26126

East Asian (EAS) AF: 0.806 AC: 31983 AN: 39700

South Asian (SAS) AF: 0.920 AC: 79355 AN: 86254

European-Finnish (FIN) AF: 0.950 AC: 50754 AN: 53418

Middle Eastern (MID) AF: 0.798 AC: 4601 AN: 5764

European-Non Finnish (NFE) AF: 0.903 AC: 1004394 AN: 1111964

Other (OTH) AF: 0.885 AC: 53449 AN: 60394

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

African (AFR) AF: 0.740 AC: 30693 AN: 41466

American (AMR) AF: 0.850 AC: 12986 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3016 AN: 3466

East Asian (EAS) AF: 0.829 AC: 4244 AN: 5122

South Asian (SAS) AF: 0.915 AC: 4403 AN: 4810

European-Finnish (FIN) AF: 0.953 AC: 10087 AN: 10580

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61592 AN: 68006

Other (OTH) AF: 0.853 AC: 1800 AN: 2110

Alfa AF: 0.877 Hom.: 55112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.52
PhyloP100		-2.8
PromoterAI		0.0057	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: rs7516762; hg19: chr1-202092580; COSMIC: COSV108219827;