chr8-53905188-T-C

Variant names:

• chr8-53905188-T-C
• rs1483537
• NM_003702.5:c.69+24104T>C

Variant summary

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

The NM_003702.5(RGS20):​c.69+24104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,226 control chromosomes in the GnomAD database, including 2,467 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 0.11 (2467 hom., cov: 32)
• Consequence: RGS20 NM_003702.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 1 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003702.5. 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
	RGS20	NM_003702.5	MANE Select	c.69+24104T>C		intron	N/A	NP_003693.2
	RGS20	NM_170587.4		c.510+25586T>C		intron	N/A	NP_733466.1
	RGS20	NM_001286673.2		c.166-34388T>C		intron	N/A	NP_001273602.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS20	ENST00000276500.5	TSL:1 MANE Select	c.69+24104T>C		intron	N/A	ENSP00000276500.4
	RGS20	ENST00000297313.8	TSL:1	c.510+25586T>C		intron	N/A	ENSP00000297313.3
	RGS20	ENST00000344277.10	TSL:1	c.166-34388T>C		intron	N/A	ENSP00000344630.6

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16033 AN: 152108 Hom.: 2463 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.0938

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

GnomAD4 genome AF: 0.106 AC: 16068 AN: 152226 Hom.: 2467 Cov.: 32 AF XY: 0.104 AC XY: 7773 AN XY: 74428

African (AFR) AF: 0.337 AC: 14001 AN: 41496

American (AMR) AF: 0.0470 AC: 718 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.118 AC: 610 AN: 5186

South Asian (SAS) AF: 0.0217 AC: 105 AN: 4828

European-Finnish (FIN) AF: 0.0190 AC: 202 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00316 AC: 215 AN: 68022

Other (OTH) AF: 0.0928 AC: 196 AN: 2112

Alfa AF: 0.0418 Hom.: 320

Bravo AF: 0.119

Asia WGS AF: 0.0920 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.91
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: rs1483537; hg19: chr8-54817748;