rs7520258

Variant names:

• chr1-236149827-T-C
• rs7520258
• NM_003272.4:c.414+6791T>C

Variant summary

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

The NM_003272.4(GPR137B):​c.414+6791T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 152,326 control chromosomes in the GnomAD database, including 854 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 0.071 (854 hom., cov: 34)
• Consequence: GPR137B NM_003272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 10 publications found

Genes affected

GPR137B (HGNC:11862): (G protein-coupled receptor 137B) Involved in several processes, including positive regulation of TORC1 signaling; positive regulation of protein localization to lysosome; and regulation of GTPase activity. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003272.4. 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
	GPR137B	NM_003272.4	MANE Select	c.414+6791T>C		intron	N/A	NP_003263.1	O60478

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR137B	ENST00000366592.8	TSL:1 MANE Select	c.414+6791T>C		intron	N/A	ENSP00000355551.3	O60478
	GPR137B	ENST00000889786.1		c.414+6791T>C		intron	N/A	ENSP00000559845.1
	GPR137B	ENST00000889783.1		c.414+6791T>C		intron	N/A	ENSP00000559842.1

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10739 AN: 152210 Hom.: 850 Cov.: 34

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.00423

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00951

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0707 AC: 10762 AN: 152326 Hom.: 854 Cov.: 34 AF XY: 0.0720 AC XY: 5367 AN XY: 74496

African (AFR) AF: 0.179 AC: 7453 AN: 41562

American (AMR) AF: 0.0561 AC: 859 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.218 AC: 1128 AN: 5176

South Asian (SAS) AF: 0.0775 AC: 374 AN: 4828

European-Finnish (FIN) AF: 0.00423 AC: 45 AN: 10628

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00951 AC: 647 AN: 68034

Other (OTH) AF: 0.0681 AC: 144 AN: 2114

Alfa AF: 0.0348 Hom.: 1083

Bravo AF: 0.0828

Asia WGS AF: 0.140 AC: 486 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.28
PhyloP100		-0.69
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: rs7520258; hg19: chr1-236313127;