4-39185530-G-C

Position:

• chr4-39185530-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_025132.4(WDR19):​c.7-196G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,938 control chromosomes in the GnomAD database, including 7,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7664 hom., cov: 32)
• Consequence: WDR19 NM_025132.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.400

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 4-39185530-G-C is Benign according to our data. Variant chr4-39185530-G-C is described in ClinVar as [Benign]. Clinvar id is 1180362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR19	NM_025132.4	c.7-196G>C		intron_variant		ENST00000399820.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR19	ENST00000399820.8	c.7-196G>C		intron_variant		1	NM_025132.4	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47814 AN: 151820 Hom.: 7653 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.315 AC: 47858 AN: 151938 Hom.: 7664 Cov.: 32 AF XY: 0.311 AC XY: 23067 AN XY: 74258

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.314

Alfa AF: 0.159 Hom.: 282

Bravo AF: 0.317

Asia WGS AF: 0.224 AC: 777 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
DANN	Benign	0.43

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: rs28639548; hg19: chr4-39187150;