chr6-153075740-T-C

Variant names:

• chr6-153075740-T-C
• rs9397585
• NM_012419.5:c.-25-31697A>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.-25-31697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,936 control chromosomes in the GnomAD database, including 13,845 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 0.42 (13845 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.964
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.-25-31697A>G		intron_variant	Intron 1 of 4	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.21-31697A>G		intron_variant	Intron 1 of 4		XP_047274590.1
RGS17	XM_047418635.1	c.9-31697A>G		intron_variant	Intron 1 of 4		XP_047274591.1
RGS17	XM_047418636.1	c.-25-31697A>G		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.-25-31697A>G		intron_variant	Intron 1 of 4	1	NM_012419.5	ENSP00000206262.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63651 AN: 151818 Hom.: 13830 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.419 AC: 63709 AN: 151936 Hom.: 13845 Cov.: 32 AF XY: 0.426 AC XY: 31613 AN XY: 74250

African (AFR) AF: 0.469 AC: 19433 AN: 41412

American (AMR) AF: 0.419 AC: 6398 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1321 AN: 3460

East Asian (EAS) AF: 0.697 AC: 3600 AN: 5162

South Asian (SAS) AF: 0.595 AC: 2861 AN: 4812

European-Finnish (FIN) AF: 0.409 AC: 4319 AN: 10562

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24564 AN: 67948

Other (OTH) AF: 0.411 AC: 867 AN: 2112

Alfa AF: 0.375 Hom.: 5469

Bravo AF: 0.418

Asia WGS AF: 0.584 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.68
PhyloP100		-0.96
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: rs9397585; hg19: chr6-153396875;