rs7750874

Positions:

• chr6-153009333-A-T

Variant summary

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

The NM_012419.5(RGS17):​c.*2241T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 151,888 control chromosomes in the GnomAD database, including 36,382 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 0.69 (36382 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RGS17 NM_012419.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

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=-0.52).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS17	NM_012419.5	c.*2241T>A		3_prime_UTR_variant	5/5	ENST00000206262.2
RGS17	XM_047418634.1	c.*2241T>A		3_prime_UTR_variant	5/5
RGS17	XM_047418635.1	c.*2241T>A		3_prime_UTR_variant	5/5
RGS17	XM_047418636.1	c.*2241T>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS17	ENST00000206262.2	c.*2241T>A		3_prime_UTR_variant	5/5	1	NM_012419.5	P1
RGS17	ENST00000367225.6	c.*2241T>A		3_prime_UTR_variant	4/4	1		P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104899 AN: 151770 Hom.: 36342 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.654

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.691 AC: 104991 AN: 151888 Hom.: 36382 Cov.: 32 AF XY: 0.693 AC XY: 51453 AN XY: 74234

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.654

Alfa AF: 0.668 Hom.: 4239

Bravo AF: 0.690

Asia WGS AF: 0.623 AC: 2161 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs7750874; hg19: chr6-153330468;