chr16-50636271-G-C

Variant names:

• chr16-50636271-G-C
• rs745230
• NM_033119.5:c.*2490G>C

Variant summary

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

The NM_033119.5(NKD1):​c.*2490G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,062 control chromosomes in the GnomAD database, including 28,287 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 0.60 (28280 hom., cov: 32)
  • Exomes 𝑓: 0.75 (7 hom.)
• Consequence: NKD1 NM_033119.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD1	NM_033119.5	MANE Select	c.*2490G>C		3_prime_UTR	Exon 10 of 10	NP_149110.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD1	ENST00000268459.6	TSL:1 MANE Select	c.*2490G>C		3_prime_UTR	Exon 10 of 10	ENSP00000268459.3

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91328 AN: 151920 Hom.: 28271 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.750 AC: 18 AN: 24 Hom.: 7 Cov.: 0 AF XY: 0.750 AC XY: 15 AN XY: 20

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.722 AC: 13 AN: 18

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.601 AC: 91368 AN: 152038 Hom.: 28280 Cov.: 32 AF XY: 0.602 AC XY: 44780 AN XY: 74334

African (AFR) AF: 0.488 AC: 20224 AN: 41434

American (AMR) AF: 0.538 AC: 8229 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2369 AN: 3470

East Asian (EAS) AF: 0.533 AC: 2751 AN: 5164

South Asian (SAS) AF: 0.453 AC: 2181 AN: 4810

European-Finnish (FIN) AF: 0.750 AC: 7930 AN: 10578

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

European-Non Finnish (NFE) AF: 0.670 AC: 45530 AN: 67982

Other (OTH) AF: 0.596 AC: 1257 AN: 2110

Alfa AF: 0.561 Hom.: 1821

Bravo AF: 0.579

Asia WGS AF: 0.490 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.43
PhyloP100		0.65
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: rs745230; hg19: chr16-50670182;