8-53867649-C-T

Position:

• chr8-53867649-C-T

Variant summary

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

The NM_170587.4(RGS20):​c.166-11609C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 151,526 control chromosomes in the GnomAD database, including 53,928 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 0.84 (53928 hom., cov: 29)
• Consequence: RGS20 NM_170587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS20	NM_170587.4	c.166-11609C>T		intron_variant		ENST00000297313.8	NP_733466.1
RGS20	NM_001286673.2	c.165+15585C>T		intron_variant			NP_001273602.1
RGS20	NM_001286675.2	c.35+15585C>T		intron_variant			NP_001273604.1
RGS20	NM_001286674.2	c.35+15585C>T		intron_variant			NP_001273603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS20	ENST00000297313.8	c.166-11609C>T		intron_variant		1	NM_170587.4	ENSP00000297313.3
RGS20	ENST00000344277.10	c.165+15585C>T		intron_variant		1		ENSP00000344630.6
RGS20	ENST00000517659.5	n.165+15585C>T		intron_variant		1		ENSP00000428795.1
RGS20	ENST00000523280.1	n.165+15585C>T		intron_variant		1		ENSP00000429897.1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127221 AN: 151408 Hom.: 53873 Cov.: 29

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.840 AC: 127332 AN: 151526 Hom.: 53928 Cov.: 29 AF XY: 0.837 AC XY: 61928 AN XY: 74024

Gnomad4 AFR AF: 0.958

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.850

Alfa AF: 0.799 Hom.: 47608

Bravo AF: 0.855

Asia WGS AF: 0.840 AC: 2917 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs1466525; hg19: chr8-54780209;