4-39255344-G-T

Position:

• chr4-39255344-G-T

Variant summary

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

The NM_025132.4(WDR19):​c.3002-504G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,994 control chromosomes in the GnomAD database, including 26,137 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 0.55 (26137 hom., cov: 31)
• Consequence: WDR19 NM_025132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

Genes affected

WDR19 (HGNC:18340): (WD repeat domain 19) The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

WDR19 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR19	NM_025132.4	c.3002-504G>T		intron_variant		ENST00000399820.8	NP_079408.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR19	ENST00000399820.8	c.3002-504G>T		intron_variant		1	NM_025132.4	ENSP00000382717.3
WDR19	ENST00000506869.5	n.*2583-504G>T		intron_variant		2		ENSP00000424319.1
WDR19	ENST00000512095.5	n.2000-504G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83483 AN: 151876 Hom.: 26122 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.550 AC: 83521 AN: 151994 Hom.: 26137 Cov.: 31 AF XY: 0.553 AC XY: 41102 AN XY: 74264

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.586

Alfa AF: 0.590 Hom.: 4202

Bravo AF: 0.539

Asia WGS AF: 0.744 AC: 2586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.52

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: rs6831700; hg19: chr4-39256964;