rs3745032

chr18-57027319-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015285.3(WDR7):c.*112C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 1,336,130 control chromosomes in the GnomAD database, including 501 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 0.021 (37 hom., cov: 32)
  • Exomes 𝑓: 0.025 (464 hom.)
• Consequence: WDR7 NM_015285.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

Genes affected

WDR7 (HGNC:13490): (WD repeat domain 7) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) that may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. The encoded protein forms the beta subunit of rabconnectin-3 and binds directly with Rab3A GDP/GTP exchange protein and indirectly with Rab3A GDP/GTP activating protein; these proteins are regulators of Rab3 small G protein family members involved in control of the calcium-dependant exocytosis of neurotransmitters. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0208 (3039/145962) while in subpopulation EAS AF= 0.0506 (260/5140). AF 95% confidence interval is 0.0455. There are 37 homozygotes in gnomad4. There are 1427 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3037 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR7	NM_015285.3	c.*112C>T		3_prime_UTR_variant	28/28	ENST00000254442.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR7	ENST00000254442.8	c.*112C>T		3_prime_UTR_variant	28/28	1	NM_015285.3	P4
WDR7	ENST00000357574.7	c.*112C>T		3_prime_UTR_variant	27/27	5		A1
WDR7	ENST00000589935.1			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3037 AN: 145852 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00656

Gnomad AMI AF: 0.0314

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.00700

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0150

GnomAD4 exome AF: 0.0254 AC: 30193 AN: 1190168 Hom.: 464 Cov.: 18 AF XY: 0.0246 AC XY: 14440 AN XY: 585964

Gnomad4 AFR exome AF: 0.00395

Gnomad4 AMR exome AF: 0.0304

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.0504

Gnomad4 SAS exome AF: 0.00571

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0194

GnomAD4 genome AF: 0.0208 AC: 3039 AN: 145962 Hom.: 37 Cov.: 32 AF XY: 0.0200 AC XY: 1427 AN XY: 71474

Gnomad4 AFR AF: 0.00654

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.00701

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0290

Gnomad4 OTH AF: 0.0149

Alfa AF: 0.0209 Hom.: 7

Bravo AF: 0.0200

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	11
Dann	Benign	0.73

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: rs3745032; hg19: chr18-54694550; COSMIC: COSV54366697; COSMIC: COSV54366697;