rs4357510

Positions:

• chr1-192643264-A-C
• chr1-192643264-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RGS13	NM_002927.5	c.-4-1067A>C		intron_variant		ENST00000391995.7
RGS13	NM_144766.3	c.-4-1067A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS13	ENST00000391995.7	c.-4-1067A>C		intron_variant		1	NM_002927.5	P1
	ENST00000644134.1	n.409-49607T>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.942

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.925

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.866

Alfa AF: 0.929 Hom.: 58982

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4357510; hg19: chr1-192612394;