4-39182549-A-G

Variant names:

• chr4-39182549-A-G
• rs60800612
• NM_025132.4:c.-9A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025132.4(WDR19):​c.-9A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00881 in 1,613,434 control chromosomes in the GnomAD database, including 1,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (536 hom., cov: 31)
  • Exomes 𝑓: 0.0049 (488 hom.)
• Consequence: WDR19 NM_025132.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.46
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P
• ciliopathy

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

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

ENSG00000249207 (HGNC:58761):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 4-39182549-A-G is Benign according to our data. Variant chr4-39182549-A-G is described in ClinVar as Benign. ClinVar VariationId is 261855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 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.-9A>G		5_prime_UTR	Exon 1 of 37	NP_079408.3
	WDR19	NM_001317924.2		c.-373A>G		5_prime_UTR	Exon 1 of 36	NP_001304853.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR19	ENST00000399820.8	TSL:1 MANE Select	c.-9A>G		5_prime_UTR	Exon 1 of 37	ENSP00000382717.3
	WDR19	ENST00000503697.5	TSL:1	n.-9A>G		non_coding_transcript_exon	Exon 1 of 9	ENSP00000423706.1
	WDR19	ENST00000503697.5	TSL:1	n.-9A>G		5_prime_UTR	Exon 1 of 9	ENSP00000423706.1

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7070 AN: 152022 Hom.: 536 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0121 AC: 2983 AN: 247062 AF XY: 0.00913

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.00848

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000754

Gnomad OTH exome AF: 0.00913

GnomAD4 exome AF: 0.00488 AC: 7134 AN: 1461294 Hom.: 488 Cov.: 31 AF XY: 0.00425 AC XY: 3090 AN XY: 726906

African (AFR) AF: 0.164 AC: 5493 AN: 33466

American (AMR) AF: 0.0100 AC: 448 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00934 AC: 53 AN: 5672

European-Non Finnish (NFE) AF: 0.000458 AC: 509 AN: 1111800

Other (OTH) AF: 0.0101 AC: 611 AN: 60346

GnomAD4 genome AF: 0.0465 AC: 7080 AN: 152140 Hom.: 536 Cov.: 31 AF XY: 0.0446 AC XY: 3318 AN XY: 74370

African (AFR) AF: 0.161 AC: 6693 AN: 41470

American (AMR) AF: 0.0164 AC: 250 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 68002

Other (OTH) AF: 0.0351 AC: 74 AN: 2110

Alfa AF: 0.0216 Hom.: 160

Bravo AF: 0.0525

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.00130

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Asphyxiating thoracic dystrophy 5 (2)
-	-	2	Cranioectodermal dysplasia 4 (2)
-	-	2	not provided (2)
-	-	1	Nephronophthisis 13 (1)
-	-	1	not specified (1)
-	-	1	Senior-Loken syndrome 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	18
DANN	Benign	0.50
PhyloP100		2.5
PromoterAI		-0.074	Neutral
Mutation Taster		=300/0	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: rs60800612; hg19: chr4-39184169;