rs7750874

Variant names:

• chr6-153009333-A-T
• rs7750874
• NM_012419.5:c.*2241T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.52).
• 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 rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.*2241T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.*2241T>A		3_prime_UTR_variant	Exon 5 of 5		XP_047274590.1
RGS17	XM_047418635.1	c.*2241T>A		3_prime_UTR_variant	Exon 5 of 5		XP_047274591.1
RGS17	XM_047418636.1	c.*2241T>A		3_prime_UTR_variant	Exon 5 of 5		XP_047274592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS17	ENST00000206262.2	c.*2241T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_012419.5	ENSP00000206262.1
RGS17	ENST00000367225.6	c.*2241T>A		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000356194.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.707 AC: 29299 AN: 41454

American (AMR) AF: 0.731 AC: 11159 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2179 AN: 3466

East Asian (EAS) AF: 0.548 AC: 2827 AN: 5160

South Asian (SAS) AF: 0.655 AC: 3162 AN: 4826

European-Finnish (FIN) AF: 0.745 AC: 7873 AN: 10562

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46143 AN: 67838

Other (OTH) AF: 0.654 AC: 1382 AN: 2114

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
PhyloP100		2.8
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: rs7750874; hg19: chr6-153330468;