6-153102117-A-G

Variant names:

• chr6-153102117-A-G
• rs487972
• NM_012419.5:c.-26+29007T>C

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+29007T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.977 in 152,308 control chromosomes in the GnomAD database, including 72,701 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 0.98 (72701 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 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.-26+29007T>C		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.-26+29007T>C		intron	N/A	ENSP00000206262.1	Q9UGC6
	RGS17	ENST00000914255.1		c.-26+29007T>C		intron	N/A	ENSP00000584314.1

Frequencies

GnomAD3 genomes AF: 0.977 AC: 148683 AN: 152190 Hom.: 72642 Cov.: 32

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.982

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

GnomAD4 genome AF: 0.977 AC: 148801 AN: 152308 Hom.: 72701 Cov.: 32 AF XY: 0.978 AC XY: 72814 AN XY: 74470

African (AFR) AF: 0.993 AC: 41293 AN: 41566

American (AMR) AF: 0.981 AC: 15008 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3435 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5165 AN: 5166

South Asian (SAS) AF: 0.993 AC: 4788 AN: 4822

European-Finnish (FIN) AF: 0.967 AC: 10267 AN: 10616

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65594 AN: 68040

Other (OTH) AF: 0.982 AC: 2077 AN: 2114

Alfa AF: 0.967 Hom.: 9556

Bravo AF: 0.978

Asia WGS AF: 0.998 AC: 3470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.6
DANN	Benign	0.76
PhyloP100		-0.29
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: rs487972; hg19: chr6-153423252;