16-50620464-A-T

Variant names:

• chr16-50620464-A-T
• rs12596811
• NM_033119.5:c.260-1138A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033119.5(NKD1):​c.260-1138A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,066 control chromosomes in the GnomAD database, including 10,179 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 0.33 (10179 hom., cov: 33)
• Consequence: NKD1 NM_033119.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKD1	NM_033119.5	c.260-1138A>T		intron_variant	Intron 4 of 9	ENST00000268459.6	NP_149110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKD1	ENST00000268459.6	c.260-1138A>T		intron_variant	Intron 4 of 9	1	NM_033119.5	ENSP00000268459.3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49429 AN: 151948 Hom.: 10160 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.325 AC: 49492 AN: 152066 Hom.: 10179 Cov.: 33 AF XY: 0.327 AC XY: 24325 AN XY: 74318

African (AFR) AF: 0.555 AC: 23010 AN: 41478

American (AMR) AF: 0.315 AC: 4811 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2775 AN: 5156

South Asian (SAS) AF: 0.500 AC: 2408 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1572 AN: 10602

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.197 AC: 13374 AN: 67960

Other (OTH) AF: 0.331 AC: 700 AN: 2114

Alfa AF: 0.261 Hom.: 825

Bravo AF: 0.350

Asia WGS AF: 0.518 AC: 1799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.94
DANN	Benign	0.77
PhyloP100		-0.17
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: rs12596811; hg19: chr16-50654375;