rs4690093

Variant names:

• chr4-3410469-A-G
• rs4690093
• NM_001394154.1:c.2021-3603A>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.2021-3603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,330 control chromosomes in the GnomAD database, including 4,993 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 (4993 hom., cov: 33)
• Consequence: RGS12 NM_001394154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS12	NM_001394154.1	c.2021-3603A>G		intron_variant	Intron 4 of 17	ENST00000336727.8	NP_001381083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS12	ENST00000336727.8	c.2021-3603A>G		intron_variant	Intron 4 of 17	1	NM_001394154.1	ENSP00000338509.4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35186 AN: 151214 Hom.: 4980 Cov.: 33

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.233 AC: 35209 AN: 151330 Hom.: 4993 Cov.: 33 AF XY: 0.235 AC XY: 17421 AN XY: 73996

African (AFR) AF: 0.0717 AC: 2921 AN: 40738

American (AMR) AF: 0.293 AC: 4474 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1028 AN: 3466

East Asian (EAS) AF: 0.477 AC: 2459 AN: 5160

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4818

European-Finnish (FIN) AF: 0.324 AC: 3425 AN: 10558

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18880 AN: 67988

Other (OTH) AF: 0.255 AC: 538 AN: 2108

Alfa AF: 0.251 Hom.: 627

Bravo AF: 0.229

Asia WGS AF: 0.347 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.39
PhyloP100		-0.42
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: rs4690093; hg19: chr4-3412196;