rs2839619

Positions:

• chr21-43016067-G-A

Variant summary

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

The NM_004571.5(PKNOX1):​c.523-841G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,018 control chromosomes in the GnomAD database, including 20,955 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 0.52 (20955 hom., cov: 33)
• Consequence: PKNOX1 NM_004571.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKNOX1	NM_004571.5	c.523-841G>A		intron_variant		ENST00000291547.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKNOX1	ENST00000291547.10	c.523-841G>A		intron_variant		1	NM_004571.5	P1
PKNOX1	ENST00000432907.6	c.172-841G>A		intron_variant		2
PKNOX1	ENST00000560448.5	c.*165-841G>A		intron_variant, NMD_transcript_variant		5
PKNOX1	ENST00000480179.1	n.582-841G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79692 AN: 151900 Hom.: 20946 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.525 AC: 79754 AN: 152018 Hom.: 20955 Cov.: 33 AF XY: 0.523 AC XY: 38887 AN XY: 74296

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.559

Alfa AF: 0.534 Hom.: 17144

Bravo AF: 0.533

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.78

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: rs2839619; hg19: chr21-44436177;