rs41262444

Variant names:

• chr22-25563735-A-G
• rs41262444
• ENST00000412773.2:n.392+622T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000412773.2(GRK3-AS1):​n.392+622T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 152,240 control chromosomes in the GnomAD database, including 17 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 0.012 (17 hom., cov: 31)
• Consequence: GRK3-AS1 ENST00000412773.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 2 publications found

Genes affected

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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0115 (1757/152240) while in subpopulation NFE AF = 0.0184 (1254/68010). AF 95% confidence interval is 0.0176. There are 17 homozygotes in GnomAd4. There are 788 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK3-AS1	NR_183556.1	n.419-254T>C		intron_variant	Intron 2 of 3
GRK3-AS1	NR_183557.1	n.422-254T>C		intron_variant	Intron 2 of 3
GRK3-AS1	NR_183558.1	n.421+355T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK3-AS1	ENST00000412773.2	n.392+622T>C		intron_variant	Intron 1 of 1	2
GRK3-AS1	ENST00000422876.2	n.390+355T>C		intron_variant	Intron 2 of 2	2
GRK3-AS1	ENST00000453811.2	n.393-254T>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1757 AN: 152122 Hom.: 17 Cov.: 31

Gnomad AFR AF: 0.00420

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0100

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

GnomAD4 genome AF: 0.0115 AC: 1757 AN: 152240 Hom.: 17 Cov.: 31 AF XY: 0.0106 AC XY: 788 AN XY: 74438

African (AFR) AF: 0.00419 AC: 174 AN: 41526

American (AMR) AF: 0.0107 AC: 163 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4818

European-Finnish (FIN) AF: 0.0115 AC: 122 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0184 AC: 1254 AN: 68010

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.0155 Hom.: 3

Bravo AF: 0.0110

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.78
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs41262444; hg19: chr22-25959702;