6-153020649-T-C

Variant names:

• chr6-153020649-T-C
• rs610614
• NM_012419.5:c.444+3613A>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.444+3613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,976 control chromosomes in the GnomAD database, including 9,768 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 0.36 (9768 hom., cov: 31)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	NM_012419.5	MANE Select	c.444+3613A>G		intron	N/A	NP_036551.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	ENST00000206262.2	TSL:1 MANE Select	c.444+3613A>G		intron	N/A	ENSP00000206262.1
	RGS17	ENST00000367225.6	TSL:1	c.444+3613A>G		intron	N/A	ENSP00000356194.1
	RGS17	ENST00000914255.1		c.354+3613A>G		intron	N/A	ENSP00000584314.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54029 AN: 151858 Hom.: 9754 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.356 AC: 54091 AN: 151976 Hom.: 9768 Cov.: 31 AF XY: 0.357 AC XY: 26507 AN XY: 74264

African (AFR) AF: 0.414 AC: 17144 AN: 41432

American (AMR) AF: 0.317 AC: 4837 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3470

East Asian (EAS) AF: 0.342 AC: 1764 AN: 5158

South Asian (SAS) AF: 0.350 AC: 1689 AN: 4820

European-Finnish (FIN) AF: 0.372 AC: 3911 AN: 10526

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22330 AN: 67972

Other (OTH) AF: 0.321 AC: 677 AN: 2112

Alfa AF: 0.359 Hom.: 3679

Bravo AF: 0.354

Asia WGS AF: 0.368 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Benign	0.54
PhyloP100		1.1
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: rs610614; hg19: chr6-153341784;