chr8-53881368-T-C

Variant names:

• chr8-53881368-T-C
• rs1384797
• NM_003702.5:c.69+284T>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+284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,930 control chromosomes in the GnomAD database, including 3,682 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 0.15 (3682 hom., cov: 31)
• Consequence: RGS20 NM_003702.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS20	NM_003702.5	MANE Select	c.69+284T>C		intron	N/A	NP_003693.2
	RGS20	NM_170587.4		c.510+1766T>C		intron	N/A	NP_733466.1	O76081-1
	RGS20	NM_001286673.2		c.165+29304T>C		intron	N/A	NP_001273602.1	O76081-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS20	ENST00000276500.5	TSL:1 MANE Select	c.69+284T>C		intron	N/A	ENSP00000276500.4	O76081-6
	RGS20	ENST00000297313.8	TSL:1	c.510+1766T>C		intron	N/A	ENSP00000297313.3	O76081-1
	RGS20	ENST00000344277.10	TSL:1	c.165+29304T>C		intron	N/A	ENSP00000344630.6	O76081-2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22446 AN: 151810 Hom.: 3645 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0952

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.148 AC: 22542 AN: 151930 Hom.: 3682 Cov.: 31 AF XY: 0.151 AC XY: 11242 AN XY: 74290

African (AFR) AF: 0.384 AC: 15912 AN: 41390

American (AMR) AF: 0.0954 AC: 1459 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 130 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1641 AN: 5094

South Asian (SAS) AF: 0.274 AC: 1313 AN: 4792

European-Finnish (FIN) AF: 0.0453 AC: 481 AN: 10608

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0192 AC: 1304 AN: 67970

Other (OTH) AF: 0.126 AC: 265 AN: 2110

Alfa AF: 0.0933 Hom.: 334

Bravo AF: 0.158

Asia WGS AF: 0.291 AC: 1012 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.8
DANN	Benign	0.23
PhyloP100		0.10
PromoterAI		0.11	Neutral
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: rs1384797; hg19: chr8-54793928;