rs2749786

Variant names:

• chr4-3313239-T-C
• rs2749786
• NM_001394154.1:c.-101-2831T>C

Variant summary

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

The NM_001394154.1(RGS12):​c.-101-2831T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,164 control chromosomes in the GnomAD database, including 4,707 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 0.23 (4707 hom., cov: 32)
• Consequence: RGS12 NM_001394154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 4 publications found

Genes affected

RGS12 (HGNC:9994): (regulator of G protein signaling 12) This gene encodes a member of the 'regulator of G protein signaling' (RGS) gene family. The encoded protein may function as a guanosine triphosphatase (GTPase)-activating protein as well as a transcriptional repressor. This protein may play a role in tumorigenesis. Multiple transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000293213 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS12	NM_001394154.1	c.-101-2831T>C		intron_variant	Intron 1 of 17	ENST00000336727.8	NP_001381083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS12	ENST00000336727.8	c.-101-2831T>C		intron_variant	Intron 1 of 17	1	NM_001394154.1	ENSP00000338509.4
RGS12	ENST00000506631.5	n.72+20140T>C		intron_variant	Intron 1 of 7	1
ENSG00000293213	ENST00000600073.1	n.*181T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35597 AN: 152046 Hom.: 4708 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.234 AC: 35588 AN: 152164 Hom.: 4707 Cov.: 32 AF XY: 0.235 AC XY: 17443 AN XY: 74370

African (AFR) AF: 0.105 AC: 4355 AN: 41532

American (AMR) AF: 0.300 AC: 4590 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 896 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1747 AN: 5180

South Asian (SAS) AF: 0.350 AC: 1688 AN: 4818

European-Finnish (FIN) AF: 0.186 AC: 1965 AN: 10576

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19410 AN: 67990

Other (OTH) AF: 0.276 AC: 582 AN: 2108

Alfa AF: 0.270 Hom.: 15687

Bravo AF: 0.234

Asia WGS AF: 0.308 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.60
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2749786; hg19: chr4-3314966;