chr18-56730391-T-C

Variant names:

• chr18-56730391-T-C
• rs17750015
• NM_015285.3:c.1775-992T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015285.3(WDR7):​c.1775-992T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,058 control chromosomes in the GnomAD database, including 6,917 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 0.29 (6917 hom., cov: 33)
• Consequence: WDR7 NM_015285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

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.1775-992T>C		intron	N/A	NP_056100.2	Q9Y4E6-1
	WDR7	NM_001382487.1		c.1775-992T>C		intron	N/A	NP_001369416.1	Q9Y4E6-1
	WDR7	NM_001382485.1		c.1775-992T>C		intron	N/A	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.1775-992T>C		intron	N/A	ENSP00000254442.3	Q9Y4E6-1
	WDR7	ENST00000357574.7	TSL:5	c.1775-992T>C		intron	N/A	ENSP00000350187.2	Q9Y4E6-2
	WDR7	ENST00000589935.1	TSL:4	c.-1+78815T>C		intron	N/A	ENSP00000467485.1	K7EPQ4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43501 AN: 151940 Hom.: 6907 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.286 AC: 43517 AN: 152058 Hom.: 6917 Cov.: 33 AF XY: 0.286 AC XY: 21232 AN XY: 74338

African (AFR) AF: 0.146 AC: 6069 AN: 41488

American (AMR) AF: 0.249 AC: 3796 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1327 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1345 AN: 5182

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4822

European-Finnish (FIN) AF: 0.347 AC: 3658 AN: 10550

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24494 AN: 67970

Other (OTH) AF: 0.321 AC: 676 AN: 2104

Alfa AF: 0.337 Hom.: 37070

Bravo AF: 0.274

Asia WGS AF: 0.294 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		1.3
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: rs17750015; hg19: chr18-54397622;