chr16-50628933-G-A

Position:

• chr16-50628933-G-A

Variant summary

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

The NM_033119.5(NKD1):​c.463-1253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 150,828 control chromosomes in the GnomAD database, including 25,814 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 0.57 (25814 hom., cov: 27)
• Consequence: NKD1 NM_033119.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

Genes affected

NKD1 (HGNC:17045): (NKD inhibitor of WNT signaling pathway 1) In the mouse, Nkd is a Dishevelled (see DVL1; MIM 601365)-binding protein that functions as a negative regulator of the Wnt (see WNT1; MIM 164820)-beta-catenin (see MIM 116806)-Tcf (see MIM 602272) signaling pathway.[supplied by OMIM, Jun 2003]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKD1	NM_033119.5	c.463-1253G>A		intron_variant		ENST00000268459.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKD1	ENST00000268459.6	c.463-1253G>A		intron_variant		1	NM_033119.5	P1
NKD1	ENST00000566396.1	n.357-1253G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85412 AN: 150716 Hom.: 25810 Cov.: 27

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.566 AC: 85435 AN: 150828 Hom.: 25814 Cov.: 27 AF XY: 0.567 AC XY: 41770 AN XY: 73606

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.566

Alfa AF: 0.594 Hom.: 4429

Bravo AF: 0.541

Asia WGS AF: 0.489 AC: 1701 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.99
DANN	Benign	0.77

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: rs1558663; hg19: chr16-50662844;