4-3313239-T-C

Position:

• chr4-3313239-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

RGS12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RGS12	NM_001394154.1	c.-101-2831T>C		intron_variant		ENST00000336727.8	NP_001381083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS12	ENST00000336727.8	c.-101-2831T>C		intron_variant		1	NM_001394154.1	ENSP00000338509.4
RGS12	ENST00000506631.5	n.72+20140T>C		intron_variant		1

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

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.276

Alfa AF: 0.283 Hom.: 6541

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2749786; hg19: chr4-3314966;