22-25563711-T-C

Variant names:

• chr22-25563711-T-C
• rs41258174
• ENST00000412773.2:n.392+646A>G

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+646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 152,206 control chromosomes in the GnomAD database, including 133 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 0.039 (133 hom., cov: 32)
• Consequence: GRK3-AS1 ENST00000412773.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 3 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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0392 (5966/152206) while in subpopulation NFE AF = 0.0427 (2907/68006). AF 95% confidence interval is 0.0414. There are 133 homozygotes in GnomAd4. There are 2816 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 133 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK3-AS1	NR_183556.1	n.419-230A>G		intron_variant	Intron 2 of 3
GRK3-AS1	NR_183557.1	n.422-230A>G		intron_variant	Intron 2 of 3
GRK3-AS1	NR_183558.1	n.421+379A>G		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+646A>G		intron_variant	Intron 1 of 1	2
GRK3-AS1	ENST00000422876.2	n.390+379A>G		intron_variant	Intron 2 of 2	2
GRK3-AS1	ENST00000453811.2	n.393-230A>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5962 AN: 152088 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0430

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

GnomAD4 genome AF: 0.0392 AC: 5966 AN: 152206 Hom.: 133 Cov.: 32 AF XY: 0.0378 AC XY: 2816 AN XY: 74408

African (AFR) AF: 0.0378 AC: 1569 AN: 41524

American (AMR) AF: 0.0251 AC: 383 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3470

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5188

South Asian (SAS) AF: 0.0361 AC: 174 AN: 4826

European-Finnish (FIN) AF: 0.0543 AC: 575 AN: 10588

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0427 AC: 2907 AN: 68006

Other (OTH) AF: 0.0426 AC: 90 AN: 2114

Alfa AF: 0.0423 Hom.: 15

Bravo AF: 0.0371

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.64
PhyloP100		0.021
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: rs41258174; hg19: chr22-25959678;