8-53874173-C-T

Variant names:

• chr8-53874173-C-T
• rs1483539
• ENST00000297313.8:c.166-5085C>T

Variant summary

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

The ENST00000297313.8(RGS20):​c.166-5085C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 151,932 control chromosomes in the GnomAD database, including 999 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 0.079 (999 hom., cov: 32)
• Consequence: RGS20 ENST00000297313.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 2 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]

ENSG00000302028 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS20	NM_170587.4	c.166-5085C>T		intron_variant	Intron 1 of 5		NP_733466.1
RGS20	NM_001286673.2	c.165+22109C>T		intron_variant	Intron 1 of 4		NP_001273602.1
RGS20	NM_001286675.2	c.35+22109C>T		intron_variant	Intron 1 of 3		NP_001273604.1
RGS20	NM_001286674.2	c.35+22109C>T		intron_variant	Intron 1 of 2		NP_001273603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS20	ENST00000297313.8	c.166-5085C>T		intron_variant	Intron 1 of 5	1		ENSP00000297313.3
RGS20	ENST00000344277.10	c.165+22109C>T		intron_variant	Intron 1 of 4	1		ENSP00000344630.6
RGS20	ENST00000517659.5	n.165+22109C>T		intron_variant	Intron 1 of 3	1		ENSP00000428795.1

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11894 AN: 151814 Hom.: 993 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0657

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

GnomAD4 genome AF: 0.0785 AC: 11929 AN: 151932 Hom.: 999 Cov.: 32 AF XY: 0.0842 AC XY: 6248 AN XY: 74222

African (AFR) AF: 0.151 AC: 6271 AN: 41402

American (AMR) AF: 0.0670 AC: 1022 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 117 AN: 3464

East Asian (EAS) AF: 0.318 AC: 1645 AN: 5166

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4822

European-Finnish (FIN) AF: 0.0441 AC: 464 AN: 10518

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0137 AC: 930 AN: 67994

Other (OTH) AF: 0.0697 AC: 147 AN: 2108

Alfa AF: 0.0297 Hom.: 276

Bravo AF: 0.0797

Asia WGS AF: 0.262 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.71
PhyloP100		-1.4
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: rs1483539; hg19: chr8-54786733;