rs3968480

Variant names:

• chr6-153111431-G-A
• rs3968480
• NM_012419.5:c.-26+19693C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-153111431-G-A
• chr6-153111431-G-T

Variant summary

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

The NM_012419.5(RGS17):​c.-26+19693C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,050 control chromosomes in the GnomAD database, including 17,232 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 0.47 (17232 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 7 publications found

Genes affected

RGS17 (HGNC:14088): (regulator of G protein signaling 17) This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing 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. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.-26+19693C>T		intron_variant	Intron 1 of 4	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.20+19608C>T		intron_variant	Intron 1 of 4		XP_047274590.1
RGS17	XM_047418635.1	c.8+13653C>T		intron_variant	Intron 1 of 4		XP_047274591.1
RGS17	XM_047418636.1	c.-26+18868C>T		intron_variant	Intron 1 of 4		XP_047274592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS17	ENST00000206262.2	c.-26+19693C>T		intron_variant	Intron 1 of 4	1	NM_012419.5	ENSP00000206262.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70998 AN: 151932 Hom.: 17229 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.467 AC: 71015 AN: 152050 Hom.: 17232 Cov.: 32 AF XY: 0.473 AC XY: 35118 AN XY: 74310

African (AFR) AF: 0.493 AC: 20455 AN: 41496

American (AMR) AF: 0.437 AC: 6675 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1740 AN: 3470

East Asian (EAS) AF: 0.852 AC: 4382 AN: 5144

South Asian (SAS) AF: 0.627 AC: 3024 AN: 4822

European-Finnish (FIN) AF: 0.442 AC: 4678 AN: 10578

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28664 AN: 67946

Other (OTH) AF: 0.474 AC: 1000 AN: 2110

Alfa AF: 0.451 Hom.: 2029

Bravo AF: 0.466

Asia WGS AF: 0.662 AC: 2295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.81
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3968480; hg19: chr6-153432566; COSMIC: COSV52810872;