1-163143470-G-T

Variant names:

• chr1-163143470-G-T
• rs1056515
• NM_003617.4:c.*3872C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

RGS5 Gene-Disease associations (from GenCC):

• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	NM_003617.4	MANE Select	c.*3872C>A		3_prime_UTR	Exon 5 of 5	NP_003608.1
	RGS5	NM_001414472.1		c.*3872C>A		3_prime_UTR	Exon 7 of 7	NP_001401401.1
	RGS5	NM_001414473.1		c.*3872C>A		3_prime_UTR	Exon 9 of 9	NP_001401402.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000313961.10	TSL:1 MANE Select	c.*3872C>A		3_prime_UTR	Exon 5 of 5	ENSP00000319308.5
	RGS5	ENST00000618415.4	TSL:4	c.*3872C>A		3_prime_UTR	Exon 6 of 6	ENSP00000480891.1
	RGS5	ENST00000469495.5	TSL:5	n.167+9080C>A		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.241 AC: 9992 AN: 41454

American (AMR) AF: 0.501 AC: 7637 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.457 AC: 2366 AN: 5172

South Asian (SAS) AF: 0.432 AC: 2082 AN: 4816

European-Finnish (FIN) AF: 0.548 AC: 5782 AN: 10554

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26318 AN: 67944

Other (OTH) AF: 0.393 AC: 830 AN: 2110

Alfa AF: 0.377 Hom.: 42097

Bravo AF: 0.362

Asia WGS AF: 0.418 AC: 1453 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.51
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1056515; hg19: chr1-163113260;