1-192643264-A-C

Variant names:

• chr1-192643264-A-C
• rs4357510
• NM_002927.5:c.-4-1067A>C

Variant summary

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

The NM_002927.5(RGS13):​c.-4-1067A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,148 control chromosomes in the GnomAD database, including 55,991 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 (55991 hom., cov: 32)
• Consequence: RGS13 NM_002927.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 4 publications found

Genes affected

RGS13 (HGNC:9995): (regulator of G protein signaling 13) The protein encoded by this gene is a member of the regulator of G protein signaling (RGS) family. RGS family members share similarity with S. cerevisiae SST2 and C. elegans egl-10 proteins, which contain a characteristic conserved RGS domain. RGS proteins accelerate GTPase activity of G protein alpha-subunits, thereby driving G protein into their inactive GDP-bound form, thus negatively regulating G protein signaling. RGS proteins have been implicated in the fine tuning of a variety of cellular events in response to G protein-coupled receptor activation. The biological function of this gene, however, is unknown. Two transcript variants encoding the same isoform exist. [provided by RefSeq, Jul 2008]

ENSG00000285280 (HGNC:49018): (RSG2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS13	NM_002927.5	c.-4-1067A>C		intron_variant	Intron 3 of 6	ENST00000391995.7	NP_002918.1
RGS13	NM_144766.3	c.-4-1067A>C		intron_variant	Intron 2 of 5		NP_658912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS13	ENST00000391995.7	c.-4-1067A>C		intron_variant	Intron 3 of 6	1	NM_002927.5	ENSP00000375853.2

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128483 AN: 152030 Hom.: 55973 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.845 AC: 128534 AN: 152148 Hom.: 55991 Cov.: 32 AF XY: 0.847 AC XY: 63011 AN XY: 74398

African (AFR) AF: 0.608 AC: 25203 AN: 41456

American (AMR) AF: 0.892 AC: 13631 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3270 AN: 3472

East Asian (EAS) AF: 0.929 AC: 4813 AN: 5182

South Asian (SAS) AF: 0.934 AC: 4510 AN: 4828

European-Finnish (FIN) AF: 0.925 AC: 9812 AN: 10604

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64325 AN: 68016

Other (OTH) AF: 0.866 AC: 1828 AN: 2110

Alfa AF: 0.916 Hom.: 76919

Bravo AF: 0.833

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.22
DANN	Benign	0.44
PhyloP100		-1.9
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: rs4357510; hg19: chr1-192612394;