chr18-56900528-A-G

Variant names:

• chr18-56900528-A-G
• rs2083020
• NM_015285.3:c.3526+20363A>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.3526+20363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,084 control chromosomes in the GnomAD database, including 51,004 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 0.82 (51004 hom., cov: 31)
• Consequence: WDR7 NM_015285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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.3526+20363A>G		intron_variant	Intron 21 of 27	ENST00000254442.8	NP_056100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR7	ENST00000254442.8	c.3526+20363A>G		intron_variant	Intron 21 of 27	1	NM_015285.3	ENSP00000254442.3
WDR7	ENST00000357574.7	c.3427+20363A>G		intron_variant	Intron 20 of 26	5		ENSP00000350187.2
WDR7	ENST00000589935.1	c.1-126476A>G		intron_variant	Intron 1 of 1	4		ENSP00000467485.1
WDR7	ENST00000586124.2	n.116+9580A>G		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.816 AC: 123966 AN: 151966 Hom.: 50968 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.816 AC: 124054 AN: 152084 Hom.: 51004 Cov.: 31 AF XY: 0.816 AC XY: 60621 AN XY: 74336

African (AFR) AF: 0.720 AC: 29834 AN: 41436

American (AMR) AF: 0.852 AC: 13014 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3113 AN: 3470

East Asian (EAS) AF: 0.982 AC: 5085 AN: 5176

South Asian (SAS) AF: 0.861 AC: 4151 AN: 4820

European-Finnish (FIN) AF: 0.775 AC: 8194 AN: 10572

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57920 AN: 68010

Other (OTH) AF: 0.836 AC: 1768 AN: 2114

Alfa AF: 0.840 Hom.: 168780

Bravo AF: 0.816

Asia WGS AF: 0.913 AC: 3175 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	0.42
DANN	Benign	0.26
PhyloP100		-0.32
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

Publications

LitVar

Other links and lift over

dbSNP: rs2083020; hg19: chr18-54567759;