chr4-39185530-G-C

Variant names:

• chr4-39185530-G-C
• rs28639548
• NM_025132.4:c.7-196G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• asphyxiating thoracic dystrophy 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cranioectodermal dysplasia 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• nephronophthisis 13

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Senior-Loken syndrome 8

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• cranioectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025132.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR19	NM_025132.4	MANE Select	c.7-196G>C		intron	N/A	NP_079408.3
	WDR19	NM_001317924.2		c.-358-196G>C		intron	N/A	NP_001304853.1	B4DGR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR19	ENST00000399820.8	TSL:1 MANE Select	c.7-196G>C		intron	N/A	ENSP00000382717.3	Q8NEZ3-1
	WDR19	ENST00000503697.5	TSL:1	n.7-196G>C		intron	N/A	ENSP00000423706.1	D6RCF7
	WDR19	ENST00000959578.1		c.7-196G>C		intron	N/A	ENSP00000629637.1

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

African (AFR) AF: 0.358 AC: 14842 AN: 41428

American (AMR) AF: 0.278 AC: 4237 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3464

East Asian (EAS) AF: 0.168 AC: 872 AN: 5178

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3143 AN: 10536

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21233 AN: 67948

Other (OTH) AF: 0.314 AC: 661 AN: 2108

Alfa AF: 0.159 Hom.: 282

Bravo AF: 0.317

Asia WGS AF: 0.224 AC: 777 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
DANN	Benign	0.43
PhyloP100		-0.40
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: rs28639548; hg19: chr4-39187150;