1-163210798-T-C

Variant names:

• chr1-163210798-T-C
• rs2940677
• ENST00000415437.1:n.408T>C

Variant summary

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

The ENST00000415437.1(RGS5-AS1):​n.408T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,142 control chromosomes in the GnomAD database, including 41,575 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 0.73 (41575 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RGS5-AS1 ENST00000415437.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 1 publications found

Genes affected

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

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5-AS1	NR_110699.1	n.408T>C		non_coding_transcript_exon_variant	Exon 4 of 4
RGS5	NM_001414472.1	c.65+37732A>G		intron_variant	Intron 3 of 6		NP_001401401.1
RGS5	NM_001414473.1	c.65+37732A>G		intron_variant	Intron 5 of 8		NP_001401402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5-AS1	ENST00000415437.1	n.408T>C		non_coding_transcript_exon_variant	Exon 4 of 4	2
RGS5	ENST00000367903.7	c.69+6728A>G		intron_variant	Intron 1 of 5	3		ENSP00000356879.3
RGS5	ENST00000618415.4	c.-280-42430A>G		intron_variant	Intron 2 of 5	4		ENSP00000480891.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111094 AN: 152022 Hom.: 41527 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.718

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.731 AC: 111193 AN: 152142 Hom.: 41575 Cov.: 32 AF XY: 0.721 AC XY: 53622 AN XY: 74368

African (AFR) AF: 0.868 AC: 36060 AN: 41522

American (AMR) AF: 0.619 AC: 9471 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2558 AN: 3468

East Asian (EAS) AF: 0.382 AC: 1972 AN: 5162

South Asian (SAS) AF: 0.685 AC: 3304 AN: 4824

European-Finnish (FIN) AF: 0.624 AC: 6589 AN: 10566

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48707 AN: 67976

Other (OTH) AF: 0.717 AC: 1515 AN: 2114

Alfa AF: 0.733 Hom.: 9072

Bravo AF: 0.733

Asia WGS AF: 0.586 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2940677; hg19: chr1-163180588;