rs41261045

Variant names:

• chr22-25564658-G-A
• rs41261045
• ENST00000412773.2:n.91C>T

Variant summary

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

The ENST00000412773.2(GRK3-AS1):​n.91C>T 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 0.0269 in 151,668 control chromosomes in the GnomAD database, including 79 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 0.027 (79 hom., cov: 31)
• Consequence: GRK3-AS1 ENST00000412773.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 2 publications found

Genes affected

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

GRK3 (HGNC:290): (G protein-coupled receptor kinase 3) The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK3	NM_005160.4	c.-383G>A		upstream_gene_variant		ENST00000324198.11	NP_005151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK3	ENST00000324198.11	c.-383G>A		upstream_gene_variant		1	NM_005160.4	ENSP00000317578.4

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4071 AN: 151552 Hom.: 78 Cov.: 31

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.0564

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00333

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.00922

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0269 AC: 4079 AN: 151668 Hom.: 79 Cov.: 31 AF XY: 0.0263 AC XY: 1946 AN XY: 74130

African (AFR) AF: 0.0526 AC: 2180 AN: 41420

American (AMR) AF: 0.0153 AC: 233 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3464

East Asian (EAS) AF: 0.00315 AC: 16 AN: 5086

South Asian (SAS) AF: 0.0581 AC: 279 AN: 4806

European-Finnish (FIN) AF: 0.00922 AC: 97 AN: 10526

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1049 AN: 67792

Other (OTH) AF: 0.0270 AC: 57 AN: 2108

Alfa AF: 0.0247 Hom.: 5

Bravo AF: 0.0287

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		-0.043
PromoterAI		-0.054	Neutral

Splicing

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

Other links and lift over

dbSNP: rs41261045; hg19: chr22-25960625;