chr6-153012415-T-C

Variant names:

• chr6-153012415-T-C
• rs503366
• NM_012419.5:c.445-653A>G

Variant summary

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

The NM_012419.5(RGS17):​c.445-653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,960 control chromosomes in the GnomAD database, including 17,369 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 0.48 (17369 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012419.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	NM_012419.5	MANE Select	c.445-653A>G		intron	N/A	NP_036551.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	ENST00000206262.2	TSL:1 MANE Select	c.445-653A>G		intron	N/A	ENSP00000206262.1
	RGS17	ENST00000367225.6	TSL:1	c.445-653A>G		intron	N/A	ENSP00000356194.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72381 AN: 151842 Hom.: 17353 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.477 AC: 72432 AN: 151960 Hom.: 17369 Cov.: 32 AF XY: 0.475 AC XY: 35294 AN XY: 74242

African (AFR) AF: 0.457 AC: 18955 AN: 41438

American (AMR) AF: 0.432 AC: 6591 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3466

East Asian (EAS) AF: 0.414 AC: 2132 AN: 5150

South Asian (SAS) AF: 0.355 AC: 1712 AN: 4820

European-Finnish (FIN) AF: 0.555 AC: 5850 AN: 10540

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33770 AN: 67962

Other (OTH) AF: 0.463 AC: 977 AN: 2108

Alfa AF: 0.400 Hom.: 2086

Bravo AF: 0.468

Asia WGS AF: 0.403 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.55
PhyloP100		-0.83
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: rs503366; hg19: chr6-153333550;