rs41259044

Variant names:

• chr22-25563844-T-G
• rs41259044
• ENST00000412773.2:n.392+513A>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+513A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 151,994 control chromosomes in the GnomAD database, including 73 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 0.028 (73 hom., cov: 31)
• Consequence: GRK3-AS1 ENST00000412773.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 1 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=-0.88).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0278 (4221/151994) while in subpopulation AFR AF = 0.0462 (1915/41420). AF 95% confidence interval is 0.0445. There are 73 homozygotes in GnomAd4. There are 2113 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 73 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK3-AS1	NR_183556.1	n.418+246A>C		intron_variant	Intron 2 of 3
GRK3-AS1	NR_183557.1	n.421+246A>C		intron_variant	Intron 2 of 3
GRK3-AS1	NR_183558.1	n.421+246A>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+513A>C		intron_variant	Intron 1 of 1	2
GRK3-AS1	ENST00000422876.2	n.390+246A>C		intron_variant	Intron 2 of 2	2
GRK3-AS1	ENST00000453811.2	n.392+246A>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4209 AN: 151876 Hom.: 74 Cov.: 31

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.0173

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0278 AC: 4221 AN: 151994 Hom.: 73 Cov.: 31 AF XY: 0.0285 AC XY: 2113 AN XY: 74268

African (AFR) AF: 0.0462 AC: 1915 AN: 41420

American (AMR) AF: 0.0141 AC: 216 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3466

East Asian (EAS) AF: 0.0374 AC: 193 AN: 5166

South Asian (SAS) AF: 0.0177 AC: 85 AN: 4798

European-Finnish (FIN) AF: 0.0408 AC: 431 AN: 10570

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0190 AC: 1288 AN: 67960

Other (OTH) AF: 0.0241 AC: 51 AN: 2112

Alfa AF: 0.0272 Hom.: 13

Bravo AF: 0.0279

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.73
PhyloP100		-0.39
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: rs41259044; hg19: chr22-25959811;