1-6251956-C-T

Variant names:

• chr1-6251956-C-T
• rs4908542
• NM_207370.4:c.787-426G>A

Variant summary

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

The NM_207370.4(GPR153):​c.787-426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,980 control chromosomes in the GnomAD database, including 28,870 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 0.59 (28870 hom., cov: 31)
• Consequence: GPR153 NM_207370.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634
• Publications: 3 publications found

Genes affected

GPR153 (HGNC:23618): (G protein-coupled receptor 153) This gene encodes an integral membrane protein that belongs to the Class A rhodopsin superfamily of G protein coupled receptors. The encoded protein is expressed primarily in the central nervous system. A knockdown of the orthologous gene in rat is associated with a significant reduction in food intake and impaired decision making ability. Mutations in this gene are associated with schizophrenia, autism, and other neuropsychiatric disorders. The expression of this gene is activated by the glioma-associated oncogene homolog 1 transcription factor which, in turn, is activated by sonic hedgehog in normal and tumorigenic cells. [provided by RefSeq, Feb 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207370.4. 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
	GPR153	NM_207370.4	MANE Select	c.787-426G>A		intron	N/A	NP_997253.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR153	ENST00000377893.3	TSL:1 MANE Select	c.787-426G>A		intron	N/A	ENSP00000367125.2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89883 AN: 151860 Hom.: 28864 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.592 AC: 89904 AN: 151980 Hom.: 28870 Cov.: 31 AF XY: 0.593 AC XY: 44076 AN XY: 74288

African (AFR) AF: 0.321 AC: 13306 AN: 41412

American (AMR) AF: 0.714 AC: 10913 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2584 AN: 3466

East Asian (EAS) AF: 0.577 AC: 2974 AN: 5158

South Asian (SAS) AF: 0.668 AC: 3222 AN: 4822

European-Finnish (FIN) AF: 0.693 AC: 7333 AN: 10576

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47476 AN: 67958

Other (OTH) AF: 0.616 AC: 1300 AN: 2110

Alfa AF: 0.669 Hom.: 43427

Bravo AF: 0.580

Asia WGS AF: 0.593 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.7
DANN	Benign	0.48
PhyloP100		0.63
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: rs4908542; hg19: chr1-6312016;