18-57027319-C-T

Variant names:

• chr18-57027319-C-T
• rs3745032
• NM_015285.3:c.*112C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3039 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015285.3. 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
	WDR7	NM_015285.3	MANE Select	c.*112C>T		3_prime_UTR	Exon 28 of 28	NP_056100.2	Q9Y4E6-1
	WDR7	NM_001382487.1		c.*112C>T		3_prime_UTR	Exon 28 of 28	NP_001369416.1	Q9Y4E6-1
	WDR7	NM_001382485.1		c.*112C>T		3_prime_UTR	Exon 27 of 27	NP_001369414.1	Q9Y4E6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR7	ENST00000254442.8	TSL:1 MANE Select	c.*112C>T		3_prime_UTR	Exon 28 of 28	ENSP00000254442.3	Q9Y4E6-1
	WDR7	ENST00000357574.7	TSL:5	c.*112C>T		3_prime_UTR	Exon 27 of 27	ENSP00000350187.2	Q9Y4E6-2
	WDR7	ENST00000589935.1	TSL:4	c.*112C>T		downstream_gene	N/A	ENSP00000467485.1	K7EPQ4

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

African (AFR) AF: 0.00395 AC: 108 AN: 27342

American (AMR) AF: 0.0304 AC: 887 AN: 29146

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 279 AN: 20166

East Asian (EAS) AF: 0.0504 AC: 1737 AN: 34458

South Asian (SAS) AF: 0.00571 AC: 375 AN: 65692

European-Finnish (FIN) AF: 0.0125 AC: 402 AN: 32250

Middle Eastern (MID) AF: 0.00189 AC: 9 AN: 4760

European-Non Finnish (NFE) AF: 0.0275 AC: 25409 AN: 925526

Other (OTH) AF: 0.0194 AC: 987 AN: 50828

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

African (AFR) AF: 0.00654 AC: 265 AN: 40490

American (AMR) AF: 0.0266 AC: 393 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 56 AN: 3300

East Asian (EAS) AF: 0.0506 AC: 260 AN: 5140

South Asian (SAS) AF: 0.00701 AC: 32 AN: 4564

European-Finnish (FIN) AF: 0.0104 AC: 105 AN: 10106

Middle Eastern (MID) AF: 0.00360 AC: 1 AN: 278

European-Non Finnish (NFE) AF: 0.0290 AC: 1869 AN: 64380

Other (OTH) AF: 0.0149 AC: 30 AN: 2018

Alfa AF: 0.0187 Hom.: 19

Bravo AF: 0.0200

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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