rs2136241

Variant names:

• chr1-163319781-C-T
• rs2136241
• ENST00000439699.1:n.132-490G>A

Variant summary

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

The NM_001414472.1(RGS5):​c.-102+1841G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,862 control chromosomes in the GnomAD database, including 21,690 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 (21690 hom., cov: 31)
• Consequence: RGS5 NM_001414472.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28
• Publications: 9 publications found

Genes affected

ENSG00000232995 (HGNC:):

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]

NUF2 (HGNC:14621): (NUF2 component of NDC80 kinetochore complex) This gene encodes a protein that is highly similar to yeast Nuf2, a component of a conserved protein complex associated with the centromere. Yeast Nuf2 disappears from the centromere during meiotic prophase when centromeres lose their connection to the spindle pole body, and plays a regulatory role in chromosome segregation. The encoded protein is found to be associated with centromeres of mitotic HeLa cells, which suggests that this protein is a functional homolog of yeast Nuf2. Alternatively spliced transcript variants that encode the same protein have been described. [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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414472.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	NM_001414472.1		c.-102+1841G>A		intron	N/A	NP_001401401.1
	RGS5	NM_001414473.1		c.-299-490G>A		intron	N/A	NP_001401402.1
	RGS5	NM_001414474.1		c.-190+1841G>A		intron	N/A	NP_001401403.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000232995	ENST00000439699.1	TSL:1	n.132-490G>A		intron	N/A
	NUF2	ENST00000534289.5	TSL:4	c.-20-6251C>T		intron	N/A	ENSP00000433533.1	E9PKH1
	RGS5	ENST00000618415.4	TSL:4	c.-378+1841G>A		intron	N/A	ENSP00000480891.1	O15539-2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81029 AN: 151744 Hom.: 21659 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.534 AC: 81116 AN: 151862 Hom.: 21690 Cov.: 31 AF XY: 0.538 AC XY: 39946 AN XY: 74210

African (AFR) AF: 0.515 AC: 21322 AN: 41410

American (AMR) AF: 0.535 AC: 8165 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1830 AN: 3462

East Asian (EAS) AF: 0.557 AC: 2866 AN: 5144

South Asian (SAS) AF: 0.540 AC: 2597 AN: 4806

European-Finnish (FIN) AF: 0.626 AC: 6599 AN: 10534

Middle Eastern (MID) AF: 0.548 AC: 159 AN: 290

European-Non Finnish (NFE) AF: 0.532 AC: 36137 AN: 67930

Other (OTH) AF: 0.504 AC: 1062 AN: 2108

Alfa AF: 0.529 Hom.: 40087

Bravo AF: 0.525

Asia WGS AF: 0.536 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.022
DANN	Benign	0.20
PhyloP100		-3.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2136241; hg19: chr1-163289571;