chr1-163150449-G-A

Position:

• chr1-163150449-G-A

Variant summary

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

The NM_003617.4(RGS5):​c.384+2101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,054 control chromosomes in the GnomAD database, including 1,424 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 0.12 (1424 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS5	NM_003617.4	c.384+2101C>T		intron_variant		ENST00000313961.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS5	ENST00000313961.10	c.384+2101C>T		intron_variant		1	NM_003617.4	P4

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18594 AN: 151938 Hom.: 1426 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0823

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.122 AC: 18586 AN: 152054 Hom.: 1424 Cov.: 32 AF XY: 0.121 AC XY: 9008 AN XY: 74332

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0825

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.119

Alfa AF: 0.134 Hom.: 244

Bravo AF: 0.113

Asia WGS AF: 0.0980 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.41

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: rs2841997; hg19: chr1-163120239;