chr16-50628933-G-A

Variant names:

• chr16-50628933-G-A
• rs1558663
• NM_033119.5:c.463-1253G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033119.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD1	NM_033119.5	MANE Select	c.463-1253G>A		intron	N/A	NP_149110.1	Q969G9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD1	ENST00000268459.6	TSL:1 MANE Select	c.463-1253G>A		intron	N/A	ENSP00000268459.3	Q969G9
	NKD1	ENST00000566396.1	TSL:3	n.357-1253G>A		intron	N/A

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

African (AFR) AF: 0.366 AC: 14972 AN: 40956

American (AMR) AF: 0.528 AC: 8029 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2348 AN: 3466

East Asian (EAS) AF: 0.557 AC: 2854 AN: 5128

South Asian (SAS) AF: 0.452 AC: 2158 AN: 4778

European-Finnish (FIN) AF: 0.746 AC: 7618 AN: 10210

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.669 AC: 45370 AN: 67768

Other (OTH) AF: 0.566 AC: 1189 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.99
DANN	Benign	0.77
PhyloP100		0.11
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: rs1558663; hg19: chr16-50662844;