6-153032723-T-C

Variant names:

• chr6-153032723-T-C
• rs516557
• NM_012419.5:c.120-6180A>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.120-6180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,004 control chromosomes in the GnomAD database, including 21,004 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 0.52 (21004 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 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.120-6180A>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.120-6180A>G		intron	N/A	ENSP00000206262.1
	RGS17	ENST00000367225.6	TSL:1	c.120-6180A>G		intron	N/A	ENSP00000356194.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79133 AN: 151886 Hom.: 20975 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.521 AC: 79217 AN: 152004 Hom.: 21004 Cov.: 32 AF XY: 0.524 AC XY: 38946 AN XY: 74292

African (AFR) AF: 0.523 AC: 21682 AN: 41462

American (AMR) AF: 0.600 AC: 9180 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1289 AN: 3468

East Asian (EAS) AF: 0.746 AC: 3854 AN: 5164

South Asian (SAS) AF: 0.627 AC: 3013 AN: 4808

European-Finnish (FIN) AF: 0.447 AC: 4717 AN: 10542

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33782 AN: 67956

Other (OTH) AF: 0.512 AC: 1082 AN: 2112

Alfa AF: 0.503 Hom.: 6621

Bravo AF: 0.533

Asia WGS AF: 0.698 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		0.68
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: rs516557; hg19: chr6-153353858;