chr1-163143470-G-T

Position:

• chr1-163143470-G-T

Variant summary

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

The NM_003617.4(RGS5):​c.*3872C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,984 control chromosomes in the GnomAD database, including 11,468 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 0.37 (11468 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RGS5 NM_003617.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.*3872C>A		3_prime_UTR_variant	5/5	ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.*3872C>A		3_prime_UTR_variant	5/5	1	NM_003617.4	ENSP00000319308	P4
RGS5	ENST00000618415.4	c.*3872C>A		3_prime_UTR_variant	6/6	4		ENSP00000480891
RGS5	ENST00000469495.5	n.167+9080C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56728 AN: 151868 Hom.: 11460 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.394

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.373 AC: 56758 AN: 151984 Hom.: 11468 Cov.: 32 AF XY: 0.384 AC XY: 28521 AN XY: 74274

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.393

Alfa AF: 0.378 Hom.: 18605

Bravo AF: 0.362

Asia WGS AF: 0.418 AC: 1453 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1056515; hg19: chr1-163113260;