rs234720

Positions:

• chr21-43025182-C-T
• chr21-43025182-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004571.5(PKNOX1):​c.926+235C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,946 control chromosomes in the GnomAD database, including 14,048 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 0.43 (14048 hom., cov: 32)
• Consequence: PKNOX1 NM_004571.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

Genes affected

PKNOX1 (HGNC:9022): (PBX/knotted 1 homeobox 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in angiogenesis and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within camera-type eye development; hemopoiesis; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKNOX1	NM_004571.5	c.926+235C>T		intron_variant		ENST00000291547.10	NP_004562.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKNOX1	ENST00000291547.10	c.926+235C>T		intron_variant		1	NM_004571.5	ENSP00000291547	P1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64776 AN: 151828 Hom.: 14051 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.427 AC: 64809 AN: 151946 Hom.: 14048 Cov.: 32 AF XY: 0.422 AC XY: 31370 AN XY: 74264

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.390

Alfa AF: 0.446 Hom.: 32686

Bravo AF: 0.412

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.055
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs234720; hg19: chr21-44445292;