Genetic Variant GRK3-AS1:n.858A>G (chr22-25562985-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000666865.2(GRK3-AS1):n.858A>G 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 0.215 in 152,118 control chromosomes in the GnomAD database, including 7,582 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 0.21 ( 7582 hom., cov: 31)

Exomes 𝑓: 0.042 ( 0 hom. )

Consequence

GRK3-AS1
ENST00000666865.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.81

Publications

4 publications found

Variant links:

Genes affected

GRK3-AS1 (HGNC:55679): (GRK3 antisense RNA 1)

GRK3-AS1 links:

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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
GRK3-AS1	NR_183556.1 link	n.597+318A>G	intron_variant	Intron 3 of 3
GRK3-AS1	NR_183557.1 link	n.600+318A>G	intron_variant	Intron 3 of 3
GRK3-AS1	NR_183558.1 link	n.421+1105A>G	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
GRK3-AS1	ENST00000666865.2 link	n.858A>G	non_coding_transcript_exon_variant	Exon 3 of 3
GRK3-AS1	ENST00000412773.2 link	n.392+1372A>G	intron_variant	Intron 1 of 1	2
GRK3-AS1	ENST00000422876.2 link	n.390+1105A>G	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32572

AN:

151976

Hom.:

7536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.0853

Gnomad FIN

AF:

0.0958

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.0652

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.0417

AC:

AN:

Hom.:

AF XY:

0.0500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.215

AC:

32677

AN:

152094

Hom.:

7582

Cov.:

AF XY:

0.210

AC XY:

15597

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.586

AC:

24295

AN:

41424

American (AMR)

AF:

0.104

AC:

1583

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

180

AN:

3468

East Asian (EAS)

AF:

0.0509

AC:

264

AN:

5188

South Asian (SAS)

AF:

0.0860

AC:

415

AN:

4826

European-Finnish (FIN)

AF:

0.0958

AC:

1015

AN:

10596

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0652

AC:

4433

AN:

67994

Other (OTH)

AF:

0.170

AC:

360

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

882

1764

2645

3527

4409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.104

Hom.:

3336

Bravo

AF:

0.232

Asia WGS

AF:

0.121

AC:

420

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.017

(source)

DANN

Benign

0.31

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over