6-153048026-T-C

Variant names:

• chr6-153048026-T-C
• rs9371276
• NM_012419.5:c.-25-3983A>G

Variant summary

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

The NM_012419.5(RGS17):​c.-25-3983A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,942 control chromosomes in the GnomAD database, including 12,111 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 0.39 (12111 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.-25-3983A>G		intron_variant	Intron 1 of 4	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.21-3983A>G		intron_variant	Intron 1 of 4		XP_047274590.1
RGS17	XM_047418635.1	c.9-3983A>G		intron_variant	Intron 1 of 4		XP_047274591.1
RGS17	XM_047418636.1	c.-25-3983A>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.-25-3983A>G		intron_variant	Intron 1 of 4	1	NM_012419.5	ENSP00000206262.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58727 AN: 151824 Hom.: 12084 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.387 AC: 58804 AN: 151942 Hom.: 12111 Cov.: 32 AF XY: 0.391 AC XY: 29071 AN XY: 74268

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.367

Alfa AF: 0.216 Hom.: 461

Bravo AF: 0.393

Asia WGS AF: 0.510 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9371276; hg19: chr6-153369161;