rs4074995

Positions:

• chr5-177370342-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.1054-249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,082 control chromosomes in the GnomAD database, including 4,444 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 0.23 (4444 hom., cov: 33)
• Consequence: RGS14 NM_006480.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS14	NM_006480.5	c.1054-249G>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.1054-249G>A		intron_variant		1	NM_006480.5	ENSP00000386229	P1
RGS14	ENST00000511890.1	c.663-246G>A		intron_variant		1		ENSP00000422329
RGS14	ENST00000425155.6	n.1158-246G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34491 AN: 151964 Hom.: 4441 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34493 AN: 152082 Hom.: 4444 Cov.: 33 AF XY: 0.229 AC XY: 17007 AN XY: 74350

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.220

Alfa AF: 0.266 Hom.: 6927

Bravo AF: 0.212

Asia WGS AF: 0.223 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4074995; hg19: chr5-176797343;