21-43028608-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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=-0.96).
• 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

African (AFR) AF: 0.246 AC: 5784 AN: 23492

American (AMR) AF: 0.0722 AC: 2542 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 1478 AN: 19786

East Asian (EAS) AF: 0.168 AC: 6277 AN: 37432

South Asian (SAS) AF: 0.119 AC: 7892 AN: 66236

European-Finnish (FIN) AF: 0.0655 AC: 3328 AN: 50788

Middle Eastern (MID) AF: 0.124 AC: 581 AN: 4670

European-Non Finnish (NFE) AF: 0.111 AC: 79584 AN: 715462

Other (OTH) AF: 0.113 AC: 5011 AN: 44274

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

African (AFR) AF: 0.241 AC: 9992 AN: 41486

American (AMR) AF: 0.0971 AC: 1483 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3468

East Asian (EAS) AF: 0.151 AC: 780 AN: 5170

South Asian (SAS) AF: 0.107 AC: 519 AN: 4828

European-Finnish (FIN) AF: 0.0546 AC: 578 AN: 10590

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7671 AN: 67994

Other (OTH) AF: 0.136 AC: 287 AN: 2108

Alfa AF: 0.121 Hom.: 4520

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
PhyloP100		-1.7
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: rs2839627; hg19: chr21-44448718;