rs1396550

Variant names:

• chr1-163253065-G-A
• rs1396550
• NM_001414472.1:c.-4-4467C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_001414472.1(RGS5):​c.-4-4467C>T variant causes a intron 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: RGS5 NM_001414472.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 4 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)

ENSG00000232995 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RGS5	NM_001414472.1	c.-4-4467C>T		intron_variant	Intron 2 of 6		NP_001401401.1
RGS5	NM_001414473.1	c.-4-4467C>T		intron_variant	Intron 4 of 8		NP_001401402.1
RGS5	NM_001414474.1	c.-4-4467C>T		intron_variant	Intron 3 of 7		NP_001401403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000618415.4	c.-281+53168C>T		intron_variant	Intron 2 of 5	4		ENSP00000480891.1
ENSG00000232995	ENST00000427213.5	n.229-4359C>T		intron_variant	Intron 2 of 2	3
RGS5	ENST00000428971.2	n.446+53168C>T		intron_variant	Intron 4 of 5	5

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

African (AFR) AF: 0.0896 AC: 3718 AN: 41504

American (AMR) AF: 0.196 AC: 2992 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3468

East Asian (EAS) AF: 0.0804 AC: 416 AN: 5174

South Asian (SAS) AF: 0.172 AC: 829 AN: 4822

European-Finnish (FIN) AF: 0.324 AC: 3414 AN: 10552

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17033 AN: 67966

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.235 Hom.: 2317

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
PhyloP100		0.43

Splicing

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

Other links and lift over

dbSNP: rs1396550; hg19: chr1-163222855;