rs41259044

chr22-25563844-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NR_183563.1(GRK3-AS1):n.604+246A>C variant causes a intron, non coding transcript 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 NR_183563.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 74 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK3-AS1	NR_183563.1	n.604+246A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK3-AS1	ENST00000668059.1	n.626+246A>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.0374

Gnomad4 SAS AF: 0.0177

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0190

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0265 Hom.: 12

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41259044; hg19: chr22-25959811;