rs9557195

Variant names:

• chr13-99304368-T-C
• rs9557195
• NM_004951.5:c.-19+2972A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004951.5(GPR183):​c.-19+2972A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,134 control chromosomes in the GnomAD database, including 2,357 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 0.16 (2357 hom., cov: 32)
• Consequence: GPR183 NM_004951.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

Genes affected

GPR183 (HGNC:3128): (G protein-coupled receptor 183) This gene was identified by the up-regulation of its expression upon Epstein-Barr virus infection of primary B lymphocytes. This gene is predicted to encode a G protein-coupled receptor that is most closely related to the thrombin receptor. Expression of this gene was detected in B-lymphocyte cell lines and lymphoid tissues but not in T-lymphocyte cell lines or peripheral blood T lymphocytes. The function of this gene is unknown. [provided by RefSeq, Jul 2008]

UBAC2 (HGNC:20486): (UBA domain containing 2) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of retrograde protein transport, ER to cytosol. Acts upstream of or within protein localization to endoplasmic reticulum. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR183	NM_004951.5	c.-19+2972A>G		intron_variant	Intron 1 of 1	ENST00000376414.5	NP_004942.1
UBAC2	NM_001144072.2	c.390-9729T>C		intron_variant	Intron 4 of 8	ENST00000403766.8	NP_001137544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR183	ENST00000376414.5	c.-19+2972A>G		intron_variant	Intron 1 of 1	1	NM_004951.5	ENSP00000365596.4
UBAC2	ENST00000403766.8	c.390-9729T>C		intron_variant	Intron 4 of 8	2	NM_001144072.2	ENSP00000383911.3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25008 AN: 152016 Hom.: 2354 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.164 AC: 25012 AN: 152134 Hom.: 2357 Cov.: 32 AF XY: 0.160 AC XY: 11905 AN XY: 74368

Gnomad4 AFR AF: 0.0892

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0578

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.199

Alfa AF: 0.200 Hom.: 1581

Bravo AF: 0.169

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.30

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: rs9557195; hg19: chr13-99956622;