chr1-163212144-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000415437.1(RGS5-AS1):​n.1754C>A 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 0.137 in 152,132 control chromosomes in the GnomAD database, including 1,499 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 0.14 ( 1499 hom., cov: 32)
Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

RGS5-AS1
ENST00000415437.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.355

Publications

5 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RGS5-AS1NR_110699.1 linkn.1754C>A non_coding_transcript_exon_variant Exon 4 of 4
RGS5NM_001414472.1 linkc.65+36386G>T intron_variant Intron 3 of 6 NP_001401401.1
RGS5NM_001414473.1 linkc.65+36386G>T intron_variant Intron 5 of 8 NP_001401402.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RGS5-AS1ENST00000415437.1 linkn.1754C>A non_coding_transcript_exon_variant Exon 4 of 4 2
RGS5ENST00000367903.7 linkc.69+5382G>T intron_variant Intron 1 of 5 3 ENSP00000356879.3 B1APM2
RGS5ENST00000618415.4 linkc.-280-43776G>T intron_variant Intron 2 of 5 4 ENSP00000480891.1 O15539-2

Frequencies

GnomAD3 genomes
AF:
0.137
AC:
20869
AN:
152008
Hom.:
1500
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.134
Gnomad AMI
AF:
0.109
Gnomad AMR
AF:
0.140
Gnomad ASJ
AF:
0.133
Gnomad EAS
AF:
0.0390
Gnomad SAS
AF:
0.0734
Gnomad FIN
AF:
0.156
Gnomad MID
AF:
0.0886
Gnomad NFE
AF:
0.149
Gnomad OTH
AF:
0.133
GnomAD4 exome
AF:
0.167
AC:
1
AN:
6
Hom.:
0
Cov.:
0
AF XY:
0.167
AC XY:
1
AN XY:
6
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
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)
AF:
0.00
AC:
0
AN:
2
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.250
AC:
1
AN:
4
Other (OTH)
AC:
0
AN:
0
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.137
AC:
20880
AN:
152126
Hom.:
1499
Cov.:
32
AF XY:
0.137
AC XY:
10156
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.133
AC:
5540
AN:
41508
American (AMR)
AF:
0.140
AC:
2135
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.133
AC:
462
AN:
3466
East Asian (EAS)
AF:
0.0387
AC:
201
AN:
5188
South Asian (SAS)
AF:
0.0738
AC:
356
AN:
4822
European-Finnish (FIN)
AF:
0.156
AC:
1649
AN:
10576
Middle Eastern (MID)
AF:
0.0918
AC:
27
AN:
294
European-Non Finnish (NFE)
AF:
0.149
AC:
10133
AN:
67970
Other (OTH)
AF:
0.132
AC:
278
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
914
1829
2743
3658
4572
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
236
472
708
944
1180
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.139
Hom.:
2535
Bravo
AF:
0.136
Asia WGS
AF:
0.0790
AC:
273
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
6.6
DANN
Benign
0.82
PhyloP100
0.35
Mutation Taster
=100/0
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs2036702; hg19: chr1-163181934; API