NM_170587.4:c.511-29817G>A

Variant names:

• chr8-53909759-G-A
• rs7824575
• NM_170587.4:c.511-29817G>A

Variant summary

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

The NM_170587.4(RGS20):​c.511-29817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,996 control chromosomes in the GnomAD database, including 15,864 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 0.41 (15864 hom., cov: 32)
• Consequence: RGS20 NM_170587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS20	NM_170587.4	c.511-29817G>A		intron_variant	Intron 2 of 5	ENST00000297313.8	NP_733466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS20	ENST00000297313.8	c.511-29817G>A		intron_variant	Intron 2 of 5	1	NM_170587.4	ENSP00000297313.3
RGS20	ENST00000276500.5	c.69+28675G>A		intron_variant	Intron 1 of 4	1		ENSP00000276500.4

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61928 AN: 151878 Hom.: 15824 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.408 AC: 62018 AN: 151996 Hom.: 15864 Cov.: 32 AF XY: 0.406 AC XY: 30190 AN XY: 74298

African (AFR) AF: 0.737 AC: 30550 AN: 41456

American (AMR) AF: 0.230 AC: 3506 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3466

East Asian (EAS) AF: 0.324 AC: 1675 AN: 5162

South Asian (SAS) AF: 0.371 AC: 1789 AN: 4816

European-Finnish (FIN) AF: 0.322 AC: 3403 AN: 10558

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19196 AN: 67958

Other (OTH) AF: 0.354 AC: 746 AN: 2110

Alfa AF: 0.313 Hom.: 36318

Bravo AF: 0.412

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.067
DANN	Benign	0.18
PhyloP100		-1.5
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: rs7824575; hg19: chr8-54822319;