18-56924640-A-G

Variant names:

• chr18-56924640-A-G
• rs8094838
• NM_015285.3:c.3713+532A>G

Variant summary

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

The NM_015285.3(WDR7):​c.3713+532A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,212 control chromosomes in the GnomAD database, including 57,020 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 0.86 (57020 hom., cov: 31)
• Consequence: WDR7 NM_015285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR7	NM_015285.3	c.3713+532A>G		intron_variant	Intron 22 of 27	ENST00000254442.8	NP_056100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR7	ENST00000254442.8	c.3713+532A>G		intron_variant	Intron 22 of 27	1	NM_015285.3	ENSP00000254442.3
WDR7	ENST00000357574.7	c.3614+532A>G		intron_variant	Intron 21 of 26	5		ENSP00000350187.2
WDR7	ENST00000589935.1	c.1-102364A>G		intron_variant	Intron 1 of 1	4		ENSP00000467485.1
WDR7	ENST00000586124.2	n.303+532A>G		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131367 AN: 152094 Hom.: 56952 Cov.: 31

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.864 AC: 131492 AN: 152212 Hom.: 57020 Cov.: 31 AF XY: 0.861 AC XY: 64091 AN XY: 74396

African (AFR) AF: 0.926 AC: 38461 AN: 41542

American (AMR) AF: 0.860 AC: 13157 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2943 AN: 3472

East Asian (EAS) AF: 0.983 AC: 5083 AN: 5172

South Asian (SAS) AF: 0.848 AC: 4088 AN: 4820

European-Finnish (FIN) AF: 0.778 AC: 8230 AN: 10578

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56764 AN: 68008

Other (OTH) AF: 0.853 AC: 1804 AN: 2116

Alfa AF: 0.847 Hom.: 50248

Bravo AF: 0.873

Asia WGS AF: 0.925 AC: 3216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.41
PhyloP100		0.79
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: rs8094838; hg19: chr18-54591871;