14-63629744-C-T

Variant names:

• chr14-63629744-C-T
• rs17750684
• NM_080666.4:c.-137-4711G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_080666.4(WDR89):​c.-137-4711G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 152,262 control chromosomes in the GnomAD database, including 33 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 0.018 (33 hom., cov: 32)
• Consequence: WDR89 NM_080666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 1 publications found

Genes affected

WDR89 (HGNC:20489): (WD repeat domain 89)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0178 (2707/152262) while in subpopulation NFE AF = 0.0271 (1843/68026). AF 95% confidence interval is 0.0261. There are 33 homozygotes in GnomAd4. There are 1356 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080666.4. 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
	WDR89	NM_080666.4	MANE Select	c.-137-4711G>A		intron	N/A	NP_542397.1
	WDR89	NM_001008726.3		c.-137-4711G>A		intron	N/A	NP_001008726.1
	WDR89	NM_001258272.2		c.-137-4711G>A		intron	N/A	NP_001245201.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR89	ENST00000620954.2	TSL:6 MANE Select	c.-137-4711G>A		intron	N/A	ENSP00000480112.1
	WDR89	ENST00000267522.7	TSL:1	c.-137-4711G>A		intron	N/A	ENSP00000267522.3
	WDR89	ENST00000394942.2	TSL:5	c.-32+12060G>A		intron	N/A	ENSP00000378399.2

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2707 AN: 152144 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00468

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0124

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

GnomAD4 genome AF: 0.0178 AC: 2707 AN: 152262 Hom.: 33 Cov.: 32 AF XY: 0.0182 AC XY: 1356 AN XY: 74452

African (AFR) AF: 0.00467 AC: 194 AN: 41548

American (AMR) AF: 0.0166 AC: 254 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4822

European-Finnish (FIN) AF: 0.0303 AC: 321 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0271 AC: 1843 AN: 68026

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.0250 Hom.: 74

Bravo AF: 0.0158

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism

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: rs17750684; hg19: chr14-64096462;