14-72270403-G-T

Variant names:

• chr14-72270403-G-T
• rs917284
• NM_001204424.2:c.85-81692G>T

Variant summary

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

The NM_001204424.2(RGS6):​c.85-81692G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,006 control chromosomes in the GnomAD database, including 24,158 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 0.56 (24158 hom., cov: 33)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.85-81692G>T		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.85-81692G>T		intron_variant	Intron 2 of 17	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85457 AN: 151888 Hom.: 24138 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.563 AC: 85521 AN: 152006 Hom.: 24158 Cov.: 33 AF XY: 0.560 AC XY: 41630 AN XY: 74278

African (AFR) AF: 0.522 AC: 21633 AN: 41442

American (AMR) AF: 0.588 AC: 8989 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2085 AN: 3468

East Asian (EAS) AF: 0.561 AC: 2899 AN: 5166

South Asian (SAS) AF: 0.509 AC: 2454 AN: 4820

European-Finnish (FIN) AF: 0.557 AC: 5878 AN: 10558

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39786 AN: 67958

Other (OTH) AF: 0.573 AC: 1206 AN: 2104

Alfa AF: 0.576 Hom.: 67608

Bravo AF: 0.561

Asia WGS AF: 0.520 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.54
PhyloP100		0.59
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: rs917284; hg19: chr14-72737111;