4-3433158-T-G

Variant names:

• chr4-3433158-T-G
• rs6818397
• NM_001394154.1:c.4114+2203T>G

Variant summary

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

The NM_001394154.1(RGS12):​c.4114+2203T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,140 control chromosomes in the GnomAD database, including 22,361 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 0.53 (22361 hom., cov: 34)
• Consequence: RGS12 NM_001394154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 16 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS12	NM_001394154.1	c.4114+2203T>G		intron_variant	Intron 17 of 17	ENST00000336727.8	NP_001381083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS12	ENST00000336727.8	c.4114+2203T>G		intron_variant	Intron 17 of 17	1	NM_001394154.1	ENSP00000338509.4

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79918 AN: 152020 Hom.: 22351 Cov.: 34

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.525 AC: 79940 AN: 152140 Hom.: 22361 Cov.: 34 AF XY: 0.531 AC XY: 39487 AN XY: 74374

African (AFR) AF: 0.326 AC: 13521 AN: 41500

American (AMR) AF: 0.550 AC: 8418 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3470

East Asian (EAS) AF: 0.501 AC: 2586 AN: 5158

South Asian (SAS) AF: 0.603 AC: 2909 AN: 4822

European-Finnish (FIN) AF: 0.728 AC: 7729 AN: 10610

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41153 AN: 67966

Other (OTH) AF: 0.512 AC: 1079 AN: 2108

Alfa AF: 0.561 Hom.: 81101

Bravo AF: 0.500

Asia WGS AF: 0.555 AC: 1930 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.63
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: rs6818397; hg19: chr4-3434885;