rs41258274

Positions:

• chr22-25563344-C-G

Variant summary

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

The ENST00000453811.1(GRK3-AS1):​n.308G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 152,262 control chromosomes in the GnomAD database, including 44 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 0.019 (44 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GRK3-AS1 ENST00000453811.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

Genes affected

GRK3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0194 (2949/152262) while in subpopulation AFR AF= 0.0326 (1354/41524). AF 95% confidence interval is 0.0312. There are 44 homozygotes in gnomad4. There are 1394 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 44 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK3-AS1	NR_183556.1	n.556G>C		non_coding_transcript_exon_variant	3/4
GRK3-AS1	NR_183557.1	n.559G>C		non_coding_transcript_exon_variant	3/4
GRK3-AS1	NR_183561.1	n.461G>C		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK3-AS1	ENST00000453811.1	n.308G>C		non_coding_transcript_exon_variant	2/3	3
GRK3-AS1	ENST00000661676.1	n.768G>C		non_coding_transcript_exon_variant	2/2
GRK3-AS1	ENST00000666865.1	n.230G>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2942 AN: 152144 Hom.: 43 Cov.: 31

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0234

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0194 AC: 2949 AN: 152262 Hom.: 44 Cov.: 31 AF XY: 0.0187 AC XY: 1394 AN XY: 74464

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0185 Hom.: 2

Bravo AF: 0.0209

Asia WGS AF: 0.0170 AC: 59 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	2.9
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41258274; hg19: chr22-25959311;