14-72388454-G-A

Position:

• chr14-72388454-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204424.2(RGS6):​c.184+36260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,134 control chromosomes in the GnomAD database, including 1,619 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 0.13 (1619 hom., cov: 32)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

Genes affected

RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

LOC105370559 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.184+36260G>A		intron_variant		ENST00000553525.6	NP_001191353.1
LOC105370559	XR_944018.3	n.335-5753C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.184+36260G>A		intron_variant		2	NM_001204424.2	ENSP00000451030	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19378 AN: 152016 Hom.: 1612 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00865

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.128 AC: 19420 AN: 152134 Hom.: 1619 Cov.: 32 AF XY: 0.126 AC XY: 9342 AN XY: 74376

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.00887

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.0723

Gnomad4 NFE AF: 0.0849

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0980 Hom.: 950

Bravo AF: 0.135

Asia WGS AF: 0.0710 AC: 247 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	1.5
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10149848; hg19: chr14-72855162;