rs2857859

Variant names:

• chr4-3320413-C-T
• rs2857859
• NM_001394154.1:c.1881+2362C>T

Variant summary

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

The NM_001394154.1(RGS12):​c.1881+2362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,112 control chromosomes in the GnomAD database, including 4,643 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 (4643 hom., cov: 33)
• Consequence: RGS12 NM_001394154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS12	NM_001394154.1	c.1881+2362C>T		intron_variant	Intron 2 of 17	ENST00000336727.8	NP_001381083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS12	ENST00000336727.8	c.1881+2362C>T		intron_variant	Intron 2 of 17	1	NM_001394154.1	ENSP00000338509.4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35182 AN: 151994 Hom.: 4644 Cov.: 33

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.231 AC: 35176 AN: 152112 Hom.: 4643 Cov.: 33 AF XY: 0.232 AC XY: 17275 AN XY: 74360

African (AFR) AF: 0.0983 AC: 4082 AN: 41522

American (AMR) AF: 0.300 AC: 4579 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 895 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1733 AN: 5160

South Asian (SAS) AF: 0.348 AC: 1676 AN: 4816

European-Finnish (FIN) AF: 0.186 AC: 1968 AN: 10576

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19311 AN: 67978

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.245 Hom.: 789

Bravo AF: 0.231

Asia WGS AF: 0.305 AC: 1058 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.50
PhyloP100		-1.6
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: rs2857859; hg19: chr4-3322140;