rs1396550

Positions:

• chr1-163253065-G-A
• chr1-163253065-G-C

Variant summary

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

The NR_182651.1(LOC127814295):​n.300-4359C>T 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 0.196 in 152,074 control chromosomes in the GnomAD database, including 3,373 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 0.20 (3373 hom., cov: 31)
• Consequence: LOC127814295 NR_182651.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC127814295	NR_182651.1	n.300-4359C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000449680.5	n.357-4359C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29815 AN: 151956 Hom.: 3369 Cov.: 31

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.196 AC: 29828 AN: 152074 Hom.: 3373 Cov.: 31 AF XY: 0.196 AC XY: 14599 AN XY: 74328

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0804

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.188

Alfa AF: 0.238 Hom.: 2122

Bravo AF: 0.182

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1396550; hg19: chr1-163222855;