21-43028608-C-T

Variant names:

• chr21-43028608-C-T
• rs2839627
• NM_004571.5:c.927-94C>T

Variant summary

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

The NM_004571.5(PKNOX1):​c.927-94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,149,458 control chromosomes in the GnomAD database, including 8,876 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 0.14 (1857 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7019 hom.)
• Consequence: PKNOX1 NM_004571.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX1	NM_004571.5	c.927-94C>T		intron_variant	Intron 9 of 10	ENST00000291547.10	NP_004562.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKNOX1	ENST00000291547.10	c.927-94C>T		intron_variant	Intron 9 of 10	1	NM_004571.5	ENSP00000291547.4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21733 AN: 152004 Hom.: 1857 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.113 AC: 112477 AN: 997336 Hom.: 7019 Cov.: 13 AF XY: 0.113 AC XY: 57600 AN XY: 509812

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0722

Gnomad4 ASJ exome AF: 0.0747

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0655

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.143 AC: 21754 AN: 152122 Hom.: 1857 Cov.: 32 AF XY: 0.138 AC XY: 10295 AN XY: 74350

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0546

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.136

Alfa AF: 0.114 Hom.: 2480

Bravo AF: 0.152

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.58

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: rs2839627; hg19: chr21-44448718;