14-105051408-C-T

Variant names:

• chr14-105051408-C-T
• rs61739168
• NM_013345.4:c.729G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_013345.4(GPR132):​c.729G>A​(p.Ser243Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,142 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (25 hom.)
• Consequence: GPR132 NM_013345.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.206
• Publications: 1 publications found

Genes affected

GPR132 (HGNC:17482): (G protein-coupled receptor 132) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein was reported to be a receptor for lysophosphatidylcholine action, but PubMedID: 15653487 retracts this finding and instead suggests this protein to be an effector of lysophosphatidylcholine action. This protein may have proton-sensing activity and may be a receptor for oxidized free fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

LINC02298 (HGNC:53216): (long intergenic non-protein coding RNA 2298)

LOC124903398 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 14-105051408-C-T is Benign according to our data. Variant chr14-105051408-C-T is described in ClinVar as Benign. ClinVar VariationId is 768681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.206 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0091 (1386/152322) while in subpopulation AFR AF = 0.0318 (1323/41562). AF 95% confidence interval is 0.0304. There are 23 homozygotes in GnomAd4. There are 636 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013345.4. 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
	GPR132	NM_013345.4	MANE Select	c.729G>A	p.Ser243Ser	synonymous	Exon 4 of 4	NP_037477.1	Q9UNW8-1
	GPR132	NM_001278694.2		c.729G>A	p.Ser243Ser	synonymous	Exon 5 of 5	NP_001265623.1	Q9UNW8-1
	GPR132	NM_001278695.2		c.702G>A	p.Ser234Ser	synonymous	Exon 3 of 3	NP_001265624.1	Q9UNW8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR132	ENST00000329797.8	TSL:1 MANE Select	c.729G>A	p.Ser243Ser	synonymous	Exon 4 of 4	ENSP00000328818.3	Q9UNW8-1
	GPR132	ENST00000392585.2	TSL:1	c.702G>A	p.Ser234Ser	synonymous	Exon 3 of 3	ENSP00000376364.2	Q9UNW8-3
	GPR132	ENST00000551869.1	TSL:1	n.*755G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000448513.1	F8VRH8

Frequencies

GnomAD3 genomes AF: 0.00907 AC: 1380 AN: 152204 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00243 AC: 611 AN: 251306 AF XY: 0.00194

Gnomad AFR exome AF: 0.0326

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000923 AC: 1349 AN: 1461820 Hom.: 25 Cov.: 32 AF XY: 0.000800 AC XY: 582 AN XY: 727204

African (AFR) AF: 0.0319 AC: 1069 AN: 33478

American (AMR) AF: 0.00174 AC: 78 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53366

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000683 AC: 76 AN: 1111998

Other (OTH) AF: 0.00182 AC: 110 AN: 60392

GnomAD4 genome AF: 0.00910 AC: 1386 AN: 152322 Hom.: 23 Cov.: 32 AF XY: 0.00854 AC XY: 636 AN XY: 74484

African (AFR) AF: 0.0318 AC: 1323 AN: 41562

American (AMR) AF: 0.00288 AC: 44 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00433 Hom.: 4

Bravo AF: 0.0104

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.0
DANN	Benign	0.54
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism

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: rs61739168; hg19: chr14-105517745;