NM_004571.5:c.523-841G>A

Variant names:

• chr21-43016067-G-A
• rs2839619
• NM_004571.5:c.523-841G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PKNOX1	NM_004571.5	c.523-841G>A		intron_variant	Intron 5 of 10	ENST00000291547.10	NP_004562.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKNOX1	ENST00000291547.10	c.523-841G>A		intron_variant	Intron 5 of 10	1	NM_004571.5	ENSP00000291547.4
PKNOX1	ENST00000432907.6	c.172-841G>A		intron_variant	Intron 4 of 9	2		ENSP00000402243.2
PKNOX1	ENST00000480179.1	n.582-841G>A		intron_variant	Intron 5 of 5	2
PKNOX1	ENST00000560448.5	n.*165-841G>A		intron_variant	Intron 3 of 8	5		ENSP00000453486.1

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

African (AFR) AF: 0.487 AC: 20187 AN: 41464

American (AMR) AF: 0.590 AC: 9007 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2635 AN: 5156

South Asian (SAS) AF: 0.503 AC: 2422 AN: 4816

European-Finnish (FIN) AF: 0.498 AC: 5269 AN: 10572

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36237 AN: 67956

Other (OTH) AF: 0.559 AC: 1181 AN: 2114

Alfa AF: 0.531 Hom.: 50237

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2839619; hg19: chr21-44436177;