rs12654812

Variant names:

• chr5-177367190-G-A
• rs12654812
• NM_006480.5:c.483+156G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-177367190-G-A
• chr5-177367190-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006480.5(RGS14):​c.483+156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,149,826 control chromosomes in the GnomAD database, including 71,030 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 0.34 (9048 hom., cov: 32)
  • Exomes 𝑓: 0.35 (61982 hom.)
• Consequence: RGS14 NM_006480.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 79 publications found

Genes affected

RGS14 (HGNC:9996): (regulator of G protein signaling 14) This gene encodes a member of the regulator of G-protein signaling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006480.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS14	NM_006480.5	MANE Select	c.483+156G>A		intron	N/A	NP_006471.2
	RGS14	NM_001366617.1		c.483+156G>A		intron	N/A	NP_001353546.1
	RGS14	NM_001366618.1		c.483+156G>A		intron	N/A	NP_001353547.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS14	ENST00000408923.8	TSL:1 MANE Select	c.483+156G>A		intron	N/A	ENSP00000386229.3
	RGS14	ENST00000511890.1	TSL:1	c.90+156G>A		intron	N/A	ENSP00000422329.1
	RGS14	ENST00000514713.5	TSL:1	n.92+156G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51956 AN: 151894 Hom.: 9039 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.347 AC: 346718 AN: 997816 Hom.: 61982 Cov.: 13 AF XY: 0.350 AC XY: 173763 AN XY: 496398

African (AFR) AF: 0.323 AC: 7648 AN: 23650

American (AMR) AF: 0.269 AC: 5782 AN: 21490

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 6418 AN: 17212

East Asian (EAS) AF: 0.309 AC: 11094 AN: 35950

South Asian (SAS) AF: 0.427 AC: 25525 AN: 59840

European-Finnish (FIN) AF: 0.365 AC: 12499 AN: 34262

Middle Eastern (MID) AF: 0.407 AC: 1219 AN: 2996

European-Non Finnish (NFE) AF: 0.345 AC: 261289 AN: 758256

Other (OTH) AF: 0.345 AC: 15244 AN: 44160

GnomAD4 genome AF: 0.342 AC: 51998 AN: 152010 Hom.: 9048 Cov.: 32 AF XY: 0.341 AC XY: 25311 AN XY: 74298

African (AFR) AF: 0.328 AC: 13613 AN: 41482

American (AMR) AF: 0.319 AC: 4867 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1281 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1267 AN: 5152

South Asian (SAS) AF: 0.416 AC: 2003 AN: 4816

European-Finnish (FIN) AF: 0.367 AC: 3880 AN: 10584

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.355 AC: 24116 AN: 67920

Other (OTH) AF: 0.327 AC: 691 AN: 2110

Alfa AF: 0.347 Hom.: 32016

Bravo AF: 0.334

Asia WGS AF: 0.326 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.1
DANN	Benign	0.96
PhyloP100		-0.077
PromoterAI		-0.082	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12654812; hg19: chr5-176794191;