chr5-177367190-G-A

Position:

• chr5-177367190-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS14	NM_006480.5	c.483+156G>A		intron_variant		ENST00000408923.8	NP_006471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS14	ENST00000408923.8	c.483+156G>A		intron_variant		1	NM_006480.5	ENSP00000386229	P1

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

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.365

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.345

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

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.327

Alfa AF: 0.351 Hom.: 12052

Bravo AF: 0.334

Asia WGS AF: 0.326 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.1
DANN	Benign	0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs12654812; hg19: chr5-176794191;