8-53954097-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_170587.4(RGS20):c.765A>G(p.Glu255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,614,016 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (30 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (37 hom.)
• Consequence: RGS20 NM_170587.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.67

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 8-53954097-A-G is Benign according to our data. Variant chr8-53954097-A-G is described in ClinVar as [Benign]. Clinvar id is 776334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1678/152292) while in subpopulation AFR AF= 0.0346 (1437/41554). AF 95% confidence interval is 0.0331. There are 30 homozygotes in gnomad4. There are 785 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 1677 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS20	NM_170587.4	c.765A>G	p.Glu255=	synonymous_variant	5/6	ENST00000297313.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS20	ENST00000297313.8	c.765A>G	p.Glu255=	synonymous_variant	5/6	1	NM_170587.4

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1677 AN: 152174 Hom.: 30 Cov.: 31

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00409 AC: 1028 AN: 251354 Hom.: 17 AF XY: 0.00314 AC XY: 426 AN XY: 135844

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.0252

Gnomad EAS exome AF: 0.000489

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000695

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00197 AC: 2885 AN: 1461724 Hom.: 37 Cov.: 31 AF XY: 0.00187 AC XY: 1359 AN XY: 727158

Gnomad4 AFR exome AF: 0.0365

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.0257

Gnomad4 EAS exome AF: 0.000453

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000442

Gnomad4 OTH exome AF: 0.00447

GnomAD4 genome AF: 0.0110 AC: 1678 AN: 152292 Hom.: 30 Cov.: 31 AF XY: 0.0105 AC XY: 785 AN XY: 74470

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.0260

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00562 Hom.: 1

Bravo AF: 0.0128

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	8.7
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs113296379; hg19: chr8-54866657; COSMIC: COSV52021501;