rs2839629

Positions:

• chr21-43032912-G-A
• chr21-43032912-G-C
• chr21-43032912-G-T

Variant summary

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

The NM_004571.5(PKNOX1):​c.*2811G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,092 control chromosomes in the GnomAD database, including 18,925 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 0.49 (18925 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PKNOX1 NM_004571.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKNOX1	NM_004571.5	c.*2811G>A		3_prime_UTR_variant	11/11	ENST00000291547.10	NP_004562.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKNOX1	ENST00000291547.10	c.*2811G>A		3_prime_UTR_variant	11/11	1	NM_004571.5	ENSP00000291547.4
PKNOX1	ENST00000432907.6	c.*2811G>A		3_prime_UTR_variant	10/10	2		ENSP00000402243.2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74838 AN: 151966 Hom.: 18925 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.492 AC: 74879 AN: 152084 Hom.: 18925 Cov.: 32 AF XY: 0.490 AC XY: 36431 AN XY: 74328

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.499

Alfa AF: 0.450 Hom.: 16093

Bravo AF: 0.498

Asia WGS AF: 0.533 AC: 1856 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	0.037
DANN	Benign	0.43

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: rs2839629; hg19: chr21-44453022;