13-94621193-G-A

Variant names:

• chr13-94621193-G-A
• rs12429818
• NM_180989.6:c.852G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_180989.6(GPR180):​c.852G>A​(p.Thr284Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,608,526 control chromosomes in the GnomAD database, including 17,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1570 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15826 hom.)
• Consequence: GPR180 NM_180989.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.238
• Publications: 10 publications found

Genes affected

GPR180 (HGNC:28899): (G protein-coupled receptor 180) This gene encodes a protein that is a member of the G protein-coupled receptor superfamily. This protein is produced predominantly in vascular smooth muscle cells and may play an important role in the regulation of vascular remodeling. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 13-94621193-G-A is Benign according to our data. Variant chr13-94621193-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059754.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_180989.6. 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
	GPR180	NM_180989.6	MANE Select	c.852G>A	p.Thr284Thr	synonymous	Exon 6 of 9	NP_851320.1	Q86V85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR180	ENST00000376958.5	TSL:1 MANE Select	c.852G>A	p.Thr284Thr	synonymous	Exon 6 of 9	ENSP00000366157.4	Q86V85
	GPR180	ENST00000936762.1		c.771G>A	p.Thr257Thr	synonymous	Exon 6 of 9	ENSP00000606821.1
	GPR180	ENST00000954032.1		c.852G>A	p.Thr284Thr	synonymous	Exon 6 of 8	ENSP00000624091.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17550 AN: 152058 Hom.: 1568 Cov.: 32

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.168 AC: 41447 AN: 246564 AF XY: 0.163

Gnomad AFR exome AF: 0.0248

Gnomad AMR exome AF: 0.384

Gnomad ASJ exome AF: 0.0534

Gnomad EAS exome AF: 0.271

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.132 AC: 192582 AN: 1456350 Hom.: 15826 Cov.: 32 AF XY: 0.134 AC XY: 97084 AN XY: 724572

African (AFR) AF: 0.0207 AC: 689 AN: 33298

American (AMR) AF: 0.366 AC: 15662 AN: 42848

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 1352 AN: 26062

East Asian (EAS) AF: 0.285 AC: 11243 AN: 39396

South Asian (SAS) AF: 0.220 AC: 18696 AN: 85150

European-Finnish (FIN) AF: 0.121 AC: 6462 AN: 53380

Middle Eastern (MID) AF: 0.101 AC: 584 AN: 5760

European-Non Finnish (NFE) AF: 0.117 AC: 129894 AN: 1110294

Other (OTH) AF: 0.133 AC: 8000 AN: 60162

GnomAD4 genome AF: 0.115 AC: 17562 AN: 152176 Hom.: 1570 Cov.: 32 AF XY: 0.121 AC XY: 8984 AN XY: 74386

African (AFR) AF: 0.0287 AC: 1191 AN: 41554

American (AMR) AF: 0.267 AC: 4069 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3472

East Asian (EAS) AF: 0.270 AC: 1394 AN: 5166

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4816

European-Finnish (FIN) AF: 0.118 AC: 1246 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7725 AN: 67992

Other (OTH) AF: 0.122 AC: 258 AN: 2112

Alfa AF: 0.114 Hom.: 3613

Bravo AF: 0.126

Asia WGS AF: 0.230 AC: 800 AN: 3478

EpiCase AF: 0.111

EpiControl AF: 0.110

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GPR180-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.3
DANN	Benign	0.73
PhyloP100		-0.24
Mutation Taster		=99/1	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: rs12429818; hg19: chr13-95273447; COSMIC: COSV65385633;