1-163163175-G-T

Position:

• chr1-163163175-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.156-1199C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,972 control chromosomes in the GnomAD database, including 25,807 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 0.56 (25807 hom., cov: 31)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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-AS1 (HGNC:40504): (RGS5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.156-1199C>A		intron_variant		ENST00000313961.10	NP_003608.1
RGS5-AS1	NR_110699.1	n.258+299G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.156-1199C>A		intron_variant		1	NM_003617.4	ENSP00000319308	P4
RGS5-AS1	ENST00000415437.1	n.258+299G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84582 AN: 151854 Hom.: 25807 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.557 AC: 84599 AN: 151972 Hom.: 25807 Cov.: 31 AF XY: 0.569 AC XY: 42230 AN XY: 74272

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.591

Alfa AF: 0.623 Hom.: 13486

Bravo AF: 0.536

Asia WGS AF: 0.624 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.81

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: rs2815287; hg19: chr1-163132965;