rs41258004

Positions:

• chr22-25564140-A-G
• chr22-25564140-A-T

Variant summary

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

The NR_183563.1(GRK3-AS1):​n.554T>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 0.0869 in 152,326 control chromosomes in the GnomAD database, including 844 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 0.087 (844 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: GRK3-AS1 NR_183563.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK3-AS1	NR_183563.1	n.554T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK3-AS1	ENST00000668059.1	n.576T>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13207 AN: 152160 Hom.: 837 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0703

GnomAD4 exome AF: 0.0208 AC: 1 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.0250 AC XY: 1 AN XY: 40

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0869 AC: 13240 AN: 152278 Hom.: 844 Cov.: 32 AF XY: 0.0858 AC XY: 6389 AN XY: 74456

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.0477

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.0872

Gnomad4 NFE AF: 0.0477

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0675 Hom.: 74

Bravo AF: 0.0875

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.47
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41258004; hg19: chr22-25960107;