rs10494390

Positions:

• chr1-163251007-T-C

Variant summary

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

The NR_182651.1(LOC127814295):​n.300-2301A>G 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 0.146 in 152,226 control chromosomes in the GnomAD database, including 1,959 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 0.15 (1959 hom., cov: 32)
• Consequence: LOC127814295 NR_182651.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC127814295	NR_182651.1	n.300-2301A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000449680.5	n.357-2301A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22273 AN: 152108 Hom.: 1958 Cov.: 32

Gnomad AFR AF: 0.0701

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0292

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.146 AC: 22284 AN: 152226 Hom.: 1959 Cov.: 32 AF XY: 0.146 AC XY: 10842 AN XY: 74416

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.0786

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.143

Alfa AF: 0.179 Hom.: 4619

Bravo AF: 0.137

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10494390; hg19: chr1-163220797;