rs16844364

Variant names:

• chr4-3436916-G-A
• rs16844364
• NM_001394154.1:c.4115-2539G>A

Variant summary

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

The NM_001394154.1(RGS12):​c.4115-2539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,240 control chromosomes in the GnomAD database, including 3,591 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 0.20 (3591 hom., cov: 33)
• Consequence: RGS12 NM_001394154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394154.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS12	NM_001394154.1	MANE Select	c.4115-2539G>A		intron	N/A	NP_001381083.1
	RGS12	NM_001394155.1		c.4115-2539G>A		intron	N/A	NP_001381084.1
	RGS12	NM_198229.3		c.4115-2539G>A		intron	N/A	NP_937872.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS12	ENST00000336727.8	TSL:1 MANE Select	c.4115-2539G>A		intron	N/A	ENSP00000338509.4
	RGS12	ENST00000344733.9	TSL:1	c.4115-2539G>A		intron	N/A	ENSP00000339381.5
	RGS12	ENST00000338806.4	TSL:1	c.2171-2539G>A		intron	N/A	ENSP00000342133.4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31139 AN: 152122 Hom.: 3588 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.205 AC: 31154 AN: 152240 Hom.: 3591 Cov.: 33 AF XY: 0.208 AC XY: 15464 AN XY: 74444

African (AFR) AF: 0.123 AC: 5125 AN: 41554

American (AMR) AF: 0.259 AC: 3959 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1001 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2320 AN: 5172

South Asian (SAS) AF: 0.309 AC: 1492 AN: 4824

European-Finnish (FIN) AF: 0.191 AC: 2023 AN: 10618

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14510 AN: 67982

Other (OTH) AF: 0.210 AC: 445 AN: 2116

Alfa AF: 0.218 Hom.: 11757

Bravo AF: 0.209

Asia WGS AF: 0.345 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.83
PhyloP100		0.087
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs16844364; hg19: chr4-3438643;