8-53943120-T-C

Variant names:

• chr8-53943120-T-C
• rs9298496
• NM_170587.4:c.659+3396T>C

Variant summary

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

The NM_170587.4(RGS20):​c.659+3396T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,060 control chromosomes in the GnomAD database, including 10,651 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 0.37 (10651 hom., cov: 32)
• Consequence: RGS20 NM_170587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 6 publications found

Genes affected

RGS20 (HGNC:14600): (regulator of G protein signaling 20) The protein encoded by this gene belongs to the family of regulator of G protein signaling (RGS) proteins, which are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound forms. This protein selectively binds to G(z)-alpha and G(alpha)-i2 subunits, and regulates their signaling activities. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS20	NM_170587.4	c.659+3396T>C		intron_variant	Intron 3 of 5	ENST00000297313.8	NP_733466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS20	ENST00000297313.8	c.659+3396T>C		intron_variant	Intron 3 of 5	1	NM_170587.4	ENSP00000297313.3
RGS20	ENST00000276500.5	c.218+3396T>C		intron_variant	Intron 2 of 4	1		ENSP00000276500.4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56211 AN: 151944 Hom.: 10642 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.370 AC: 56256 AN: 152060 Hom.: 10651 Cov.: 32 AF XY: 0.377 AC XY: 28029 AN XY: 74332

African (AFR) AF: 0.370 AC: 15336 AN: 41450

American (AMR) AF: 0.286 AC: 4367 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3464

East Asian (EAS) AF: 0.428 AC: 2218 AN: 5186

South Asian (SAS) AF: 0.585 AC: 2823 AN: 4826

European-Finnish (FIN) AF: 0.462 AC: 4873 AN: 10556

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24430 AN: 67990

Other (OTH) AF: 0.342 AC: 723 AN: 2112

Alfa AF: 0.346 Hom.: 9738

Bravo AF: 0.352

Asia WGS AF: 0.444 AC: 1543 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.69
PhyloP100		-0.20
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: rs9298496; hg19: chr8-54855680;