22-25562985-T-C

Variant summary

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

The NR_183563.1(GRK3-AS1):n.783+318A>G variant causes a intron, non coding transcript 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 NR_183563.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK3-AS1	NR_183563.1	n.783+318A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK3-AS1	ENST00000668059.1	n.626+1105A>G		intron_variant, non_coding_transcript_variant
GRK3-AS1	ENST00000666865.1	n.589A>G		non_coding_transcript_exon_variant	2/2
GRK3-AS1	ENST00000412773.1	n.106+1372A>G		intron_variant, non_coding_transcript_variant		2
GRK3-AS1	ENST00000422876.1	n.61+1105A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32572 AN: 151976 Hom.: 7536 Cov.: 31

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: 1 AN: 24 Hom.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.215 AC: 32677 AN: 152094 Hom.: 7582 Cov.: 31 AF XY: 0.210 AC XY: 15597 AN XY: 74344

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.0509

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.0958

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.170

Alfa AF: 0.0870 Hom.: 1673

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
Dann	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2205971; hg19: chr22-25958952;