chr14-31483548-G-A

Variant names:

• chr14-31483548-G-A
• rs17097921
• NM_001197184.3:c.418C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001197184.3(GPR33):​c.418C>T​(p.Arg140*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,536,160 control chromosomes in the GnomAD database, including 759,337 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 0.99 (74770 hom., cov: 33)
  • Exomes 𝑓: 0.99 (684567 hom.)
• Consequence: GPR33 NM_001197184.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• Publications: 7 publications found

Genes affected

GPR33 (HGNC:4489): (G protein-coupled receptor 33) This gene has been identified as an orphan chemoattractant G-protein-coupled receptors (GPCR) pseudogene. Studies have shown that the inactivated gene is present as the predominant allele in the human population. A small fraction of the human population has been found to harbor an intact allele.[provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR33	NM_001197184.3	c.418C>T	p.Arg140*	stop_gained	Exon 2 of 2	ENST00000399285.5	NP_001184113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR33	ENST00000399285.5	c.418C>T	p.Arg140*	stop_gained	Exon 2 of 2	1	NM_001197184.3	ENSP00000421557.1

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150806 AN: 152222 Hom.: 74715 Cov.: 33

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.958

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.986

GnomAD4 exome AF: 0.995 AC: 1376281 AN: 1383820 Hom.: 684567 Cov.: 90 AF XY: 0.994 AC XY: 678618 AN XY: 682850

African (AFR) AF: 0.986 AC: 31149 AN: 31594

American (AMR) AF: 0.997 AC: 35603 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 25043 AN: 25180

East Asian (EAS) AF: 0.935 AC: 33403 AN: 35734

South Asian (SAS) AF: 0.967 AC: 76589 AN: 79236

European-Finnish (FIN) AF: 0.999 AC: 33856 AN: 33892

Middle Eastern (MID) AF: 0.992 AC: 5648 AN: 5696

European-Non Finnish (NFE) AF: 0.999 AC: 1077736 AN: 1078884

Other (OTH) AF: 0.989 AC: 57254 AN: 57904

GnomAD4 genome AF: 0.991 AC: 150920 AN: 152340 Hom.: 74770 Cov.: 33 AF XY: 0.991 AC XY: 73790 AN XY: 74488

African (AFR) AF: 0.985 AC: 40940 AN: 41572

American (AMR) AF: 0.994 AC: 15211 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3459 AN: 3472

East Asian (EAS) AF: 0.935 AC: 4837 AN: 5176

South Asian (SAS) AF: 0.959 AC: 4628 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10627 AN: 10628

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67955 AN: 68046

Other (OTH) AF: 0.984 AC: 2081 AN: 2114

Alfa AF: 0.996 Hom.: 116046

Bravo AF: 0.990

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Pathogenic	37
PhyloP100		2.2
Vest4		0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17097921; hg19: chr14-31952754;