chr1-163148262-G-A

Variant names:

• chr1-163148262-G-A
• rs2344673
• NM_003617.4:c.385-759C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003617.4(RGS5):​c.385-759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 151,920 control chromosomes in the GnomAD database, including 913 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 0.093 (913 hom., cov: 30)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	NM_003617.4	MANE Select	c.385-759C>T		intron	N/A	NP_003608.1	O15539-1
	RGS5	NM_001414472.1		c.406-759C>T		intron	N/A	NP_001401401.1
	RGS5	NM_001414473.1		c.406-759C>T		intron	N/A	NP_001401402.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000313961.10	TSL:1 MANE Select	c.385-759C>T		intron	N/A	ENSP00000319308.5	O15539-1
	RGS5	ENST00000527988.1	TSL:1	c.61-759C>T		intron	N/A	ENSP00000432313.1	O15539-2
	RGS5	ENST00000367903.7	TSL:3	c.445-759C>T		intron	N/A	ENSP00000356879.3	B1APM2

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14109 AN: 151802 Hom.: 912 Cov.: 30

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0929 AC: 14107 AN: 151920 Hom.: 913 Cov.: 30 AF XY: 0.0878 AC XY: 6515 AN XY: 74242

African (AFR) AF: 0.0272 AC: 1125 AN: 41414

American (AMR) AF: 0.0997 AC: 1520 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4812

European-Finnish (FIN) AF: 0.0791 AC: 833 AN: 10534

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9625 AN: 67970

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.105 Hom.: 430

Bravo AF: 0.0949

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.62
PhyloP100		0.30
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: rs2344673; hg19: chr1-163118052;