rs41261045

Variant names:

• chr22-25564658-G-A
• rs41261045
• ENST00000869559.1:c.-10+144G>A

Variant summary

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

The ENST00000869559.1(GRK3):​c.-10+144G>A variant causes a intron 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 ENST00000869559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 2 publications found

Genes affected

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]

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000869559.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK3-AS1	NR_183560.1		n.75C>T		non_coding_transcript_exon	Exon 1 of 2
	GRK3-AS1	NR_183567.1		n.75C>T		non_coding_transcript_exon	Exon 1 of 2
	GRK3-AS1	NR_183556.1		n.151+78C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK3	ENST00000869559.1		c.-10+144G>A		intron	N/A	ENSP00000539618.1
	GRK3-AS1	ENST00000412773.2	TSL:2	n.91C>T		non_coding_transcript_exon	Exon 1 of 2
	GRK3-AS1	ENST00000661676.2		n.105C>T		non_coding_transcript_exon	Exon 1 of 2

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41261045;

hg19: chr22-25960625;