chr14-72349918-T-C

Variant names:

• chr14-72349918-T-C
• rs2681749
• NM_001204424.2:c.85-2177T>C

Variant summary

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

The NM_001204424.2(RGS6):​c.85-2177T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,040 control chromosomes in the GnomAD database, including 21,855 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 0.51 (21855 hom., cov: 32)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.85-2177T>C		intron_variant	Intron 2 of 17	ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.85-2177T>C		intron_variant	Intron 2 of 17	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77860 AN: 151922 Hom.: 21809 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.513 AC: 77966 AN: 152040 Hom.: 21855 Cov.: 32 AF XY: 0.515 AC XY: 38275 AN XY: 74336

African (AFR) AF: 0.751 AC: 31134 AN: 41442

American (AMR) AF: 0.440 AC: 6718 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3466

East Asian (EAS) AF: 0.278 AC: 1438 AN: 5170

South Asian (SAS) AF: 0.603 AC: 2900 AN: 4812

European-Finnish (FIN) AF: 0.453 AC: 4785 AN: 10570

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28086 AN: 67994

Other (OTH) AF: 0.483 AC: 1019 AN: 2110

Alfa AF: 0.494 Hom.: 4457

Bravo AF: 0.516

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.090
Mutation Taster		=100/0	polymorphism (auto)

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: rs2681749; hg19: chr14-72816626;