rs7549021

chr1-163191673-A-Gchr1-163191673-A-T

Variant summary

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

The NM_003617.4(RGS5):c.44+11119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,040 control chromosomes in the GnomAD database, including 4,133 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 0.22 (4133 hom., cov: 31)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS5	NM_003617.4	c.44+11119T>C		intron_variant		ENST00000313961.10
RGS5-AS1	NR_110699.1	n.259-15024A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS5	ENST00000313961.10	c.44+11119T>C		intron_variant		1	NM_003617.4	P4
RGS5-AS1	ENST00000415437.1	n.259-15024A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32847 AN: 151922 Hom.: 4121 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.216 AC: 32892 AN: 152040 Hom.: 4133 Cov.: 31 AF XY: 0.217 AC XY: 16113 AN XY: 74346

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.205

Alfa AF: 0.0787 Hom.: 96

Bravo AF: 0.219

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.4
Dann	Benign	0.37

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: rs7549021; hg19: chr1-163161463;