rs2999967

Variant names:

• chr1-163196886-G-A
• rs2999967
• NM_003617.4:c.44+5906C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-163196886-G-A
• chr1-163196886-G-T

Variant summary

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

The NM_003617.4(RGS5):​c.44+5906C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,040 control chromosomes in the GnomAD database, including 23,551 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 0.55 (23551 hom., cov: 33)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262
• Publications: 2 publications found

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

RGS5-AS1 (HGNC:40504): (RGS5 antisense RNA 1)

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 (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003617.4. 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
	RGS5	NM_003617.4	MANE Select	c.44+5906C>T		intron	N/A	NP_003608.1
	RGS5	NM_001414472.1		c.66-28518C>T		intron	N/A	NP_001401401.1
	RGS5	NM_001414473.1		c.66-28518C>T		intron	N/A	NP_001401402.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000313961.10	TSL:1 MANE Select	c.44+5906C>T		intron	N/A	ENSP00000319308.5
	RGS5	ENST00000527988.1	TSL:1	c.-108+5906C>T		intron	N/A	ENSP00000432313.1
	RGS5	ENST00000367903.7	TSL:3	c.69+20640C>T		intron	N/A	ENSP00000356879.3

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83145 AN: 151922 Hom.: 23529 Cov.: 33

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.547 AC: 83212 AN: 152040 Hom.: 23551 Cov.: 33 AF XY: 0.542 AC XY: 40253 AN XY: 74322

African (AFR) AF: 0.693 AC: 28769 AN: 41484

American (AMR) AF: 0.429 AC: 6546 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3466

East Asian (EAS) AF: 0.284 AC: 1463 AN: 5152

South Asian (SAS) AF: 0.547 AC: 2637 AN: 4818

European-Finnish (FIN) AF: 0.462 AC: 4887 AN: 10574

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35248 AN: 67966

Other (OTH) AF: 0.513 AC: 1082 AN: 2108

Alfa AF: 0.525 Hom.: 10717

Bravo AF: 0.545

Asia WGS AF: 0.463 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.53
PhyloP100		0.26
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: rs2999967; hg19: chr1-163166676;