13-94612350-C-T

Variant names:

• chr13-94612350-C-T
• rs9524559
• NM_180989.6:c.465C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_180989.6(GPR180):​c.465C>T​(p.Ala155Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,608,524 control chromosomes in the GnomAD database, including 105,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.31 (7759 hom., cov: 32)
  • Exomes 𝑓: 0.36 (98086 hom.)
• Consequence: GPR180 NM_180989.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.24
• Publications: 33 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 13-94612350-C-T is Benign according to our data. Variant chr13-94612350-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060414.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 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.465C>T	p.Ala155Ala	synonymous	Exon 3 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.465C>T	p.Ala155Ala	synonymous	Exon 3 of 9	ENSP00000366157.4	Q86V85
	GPR180	ENST00000936762.1		c.384C>T	p.Ala128Ala	synonymous	Exon 3 of 9	ENSP00000606821.1
	GPR180	ENST00000954032.1		c.465C>T	p.Ala155Ala	synonymous	Exon 3 of 8	ENSP00000624091.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46674 AN: 151794 Hom.: 7759 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.315

GnomAD2 exomes AF: 0.330 AC: 82822 AN: 251282 AF XY: 0.337

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.309

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.363 AC: 529379 AN: 1456612 Hom.: 98086 Cov.: 32 AF XY: 0.363 AC XY: 263408 AN XY: 724950

African (AFR) AF: 0.177 AC: 5923 AN: 33426

American (AMR) AF: 0.242 AC: 10840 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 8266 AN: 26098

East Asian (EAS) AF: 0.333 AC: 13190 AN: 39636

South Asian (SAS) AF: 0.343 AC: 29569 AN: 86128

European-Finnish (FIN) AF: 0.352 AC: 18782 AN: 53404

Middle Eastern (MID) AF: 0.319 AC: 1836 AN: 5750

European-Non Finnish (NFE) AF: 0.379 AC: 420010 AN: 1107230

Other (OTH) AF: 0.348 AC: 20963 AN: 60234

GnomAD4 genome AF: 0.307 AC: 46680 AN: 151912 Hom.: 7759 Cov.: 32 AF XY: 0.307 AC XY: 22773 AN XY: 74242

African (AFR) AF: 0.182 AC: 7545 AN: 41376

American (AMR) AF: 0.278 AC: 4250 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1694 AN: 5166

South Asian (SAS) AF: 0.333 AC: 1604 AN: 4822

European-Finnish (FIN) AF: 0.351 AC: 3699 AN: 10524

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.379 AC: 25755 AN: 67974

Other (OTH) AF: 0.317 AC: 666 AN: 2102

Alfa AF: 0.349 Hom.: 16090

Bravo AF: 0.294

Asia WGS AF: 0.316 AC: 1097 AN: 3478

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	-0.46
CADD	Benign	0.061
DANN	Benign	0.69
PhyloP100		-1.2
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: rs9524559; hg19: chr13-95264604; COSMIC: COSV65385336;