chr22-23568559-G-A

Position:

• chr22-23568559-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000458318.2(ENSG00000224277):​n.308-1G>A variant causes a splice acceptor, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,242 control chromosomes in the GnomAD database, including 19,108 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 0.42 (19107 hom., cov: 30)
  • Exomes 𝑓: 0.31 (1 hom.)
• Consequence: ENST00000458318.2 splice_acceptor, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

Genes affected

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372957	XR_938078.2	n.1129-1G>A		splice_acceptor_variant, non_coding_transcript_variant
LOC105372957	XR_938075.2	n.1129-1G>A		splice_acceptor_variant, non_coding_transcript_variant
LOC105372957	XR_938076.1	n.610-1G>A		splice_acceptor_variant, non_coding_transcript_variant
LOC105372957	XR_938077.2	n.1129-1G>A		splice_acceptor_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000458318.2	n.308-1G>A		splice_acceptor_variant, non_coding_transcript_variant		3
	ENST00000454863.4	n.308-1G>A		splice_acceptor_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63318 AN: 151108 Hom.: 19049 Cov.: 30

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.308 AC: 8 AN: 26 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 5 AN XY: 20

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.420 AC: 63442 AN: 151216 Hom.: 19107 Cov.: 30 AF XY: 0.419 AC XY: 30917 AN XY: 73794

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.390

Alfa AF: 0.336 Hom.: 3936

Bravo AF: 0.453

Asia WGS AF: 0.483 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8138979; hg19: chr22-23910746;