rs685449

Variant names:

• chr6-153023396-T-A
• rs685449
• NM_012419.5:c.444+866A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-153023396-T-A
• chr6-153023396-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000206262.2(RGS17):​c.444+866A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 507,118 control chromosomes in the GnomAD database, including 46,524 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 0.43 (13878 hom., cov: 32)
  • Exomes 𝑓: 0.42 (32646 hom.)
• Consequence: RGS17 ENST00000206262.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000206262.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	NM_012419.5	MANE Select	c.444+866A>T		intron	N/A	NP_036551.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	ENST00000206262.2	TSL:1 MANE Select	c.444+866A>T		intron	N/A	ENSP00000206262.1
	RGS17	ENST00000367225.6	TSL:1	c.444+866A>T		intron	N/A	ENSP00000356194.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64565 AN: 151956 Hom.: 13856 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.380

GnomAD2 exomes AF: 0.426 AC: 96726 AN: 227128 AF XY: 0.429

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.463

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.402

GnomAD4 exome AF: 0.424 AC: 150387 AN: 355044 Hom.: 32646 Cov.: 0 AF XY: 0.430 AC XY: 87935 AN XY: 204420

African (AFR) AF: 0.448 AC: 4600 AN: 10264

American (AMR) AF: 0.402 AC: 14433 AN: 35904

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 4363 AN: 11300

East Asian (EAS) AF: 0.473 AC: 6141 AN: 12976

South Asian (SAS) AF: 0.528 AC: 34207 AN: 64828

European-Finnish (FIN) AF: 0.419 AC: 6880 AN: 16412

Middle Eastern (MID) AF: 0.419 AC: 1170 AN: 2794

European-Non Finnish (NFE) AF: 0.390 AC: 72031 AN: 184582

Other (OTH) AF: 0.411 AC: 6562 AN: 15984

GnomAD4 genome AF: 0.425 AC: 64635 AN: 152074 Hom.: 13878 Cov.: 32 AF XY: 0.428 AC XY: 31824 AN XY: 74332

African (AFR) AF: 0.459 AC: 19034 AN: 41494

American (AMR) AF: 0.405 AC: 6189 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3468

East Asian (EAS) AF: 0.454 AC: 2336 AN: 5146

South Asian (SAS) AF: 0.537 AC: 2596 AN: 4830

European-Finnish (FIN) AF: 0.443 AC: 4679 AN: 10570

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26957 AN: 67964

Other (OTH) AF: 0.386 AC: 815 AN: 2110

Alfa AF: 0.380 Hom.: 6630

Bravo AF: 0.421

Asia WGS AF: 0.527 AC: 1832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.48
PhyloP100		0.27
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: rs685449; hg19: chr6-153344531;