rs746702

Positions:

• chr16-50608543-T-C

Variant summary

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

The NM_033119.5(NKD1):​c.259+183T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 629,242 control chromosomes in the GnomAD database, including 1,393 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 0.075 (966 hom., cov: 32)
  • Exomes 𝑓: 0.024 (427 hom.)
• Consequence: NKD1 NM_033119.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

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]

ENSG00000205414 (HGNC:58215):

LOC124903773 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKD1	NM_033119.5	c.259+183T>C		intron_variant		ENST00000268459.6	NP_149110.1
LOC124903773	XR_007065197.1	n.61-93A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKD1	ENST00000268459.6	c.259+183T>C		intron_variant		1	NM_033119.5	ENSP00000268459.3
ENSG00000205414	ENST00000379963.1	n.95-93A>G		intron_variant		2
NKD1	ENST00000564336.1	n.417+183T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11296 AN: 151944 Hom.: 948 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.00892

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0637

GnomAD4 exome AF: 0.0244 AC: 11642 AN: 477180 Hom.: 427 AF XY: 0.0222 AC XY: 5609 AN XY: 252264

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.0497

Gnomad4 ASJ exome AF: 0.0313

Gnomad4 EAS exome AF: 0.0236

Gnomad4 SAS exome AF: 0.00851

Gnomad4 FIN exome AF: 0.0213

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0298

GnomAD4 genome AF: 0.0747 AC: 11356 AN: 152062 Hom.: 966 Cov.: 32 AF XY: 0.0728 AC XY: 5411 AN XY: 74360

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.0300

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0552 Hom.: 98

Bravo AF: 0.0825

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.44
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.9

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: rs746702; hg19: chr16-50642454;