rs2136241

Positions:

• chr1-163319781-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_182651.1(LOC127814295):​n.114+1841G>A variant causes a intron, non coding transcript 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: LOC127814295 NR_182651.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28

Genes affected

(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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC127814295	NR_182651.1	n.114+1841G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000449680.5	n.171+1841G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.504

Alfa AF: 0.530 Hom.: 29233

Bravo AF: 0.525

Asia WGS AF: 0.536 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2136241; hg19: chr1-163289571;