6-153110241-G-C

Variant names:

• chr6-153110241-G-C
• rs1281962
• NM_012419.5:c.-26+20883C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012419.5(RGS17):​c.-26+20883C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,908 control chromosomes in the GnomAD database, including 30,368 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 0.62 (30368 hom., cov: 31)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.-26+20883C>G		intron_variant	Intron 1 of 4	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.20+20798C>G		intron_variant	Intron 1 of 4		XP_047274590.1
RGS17	XM_047418635.1	c.8+14843C>G		intron_variant	Intron 1 of 4		XP_047274591.1
RGS17	XM_047418636.1	c.-26+20058C>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.-26+20883C>G		intron_variant	Intron 1 of 4	1	NM_012419.5	ENSP00000206262.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94337 AN: 151790 Hom.: 30321 Cov.: 31

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.622 AC: 94445 AN: 151908 Hom.: 30368 Cov.: 31 AF XY: 0.627 AC XY: 46506 AN XY: 74212

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.614

Alfa AF: 0.592 Hom.: 3361

Bravo AF: 0.625

Asia WGS AF: 0.770 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1281962; hg19: chr6-153431376; COSMIC: COSV52810851;