rs2576415

Variant names:

• chr18-56849149-T-A
• rs2576415
• NM_015285.3:c.3305-30795T>A

Variant summary

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

The NM_015285.3(WDR7):​c.3305-30795T>A 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 152,006 control chromosomes in the GnomAD database, including 7,990 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 (7990 hom., cov: 32)
• Consequence: WDR7 NM_015285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR7	NM_015285.3	c.3305-30795T>A		intron_variant	Intron 20 of 27	ENST00000254442.8	NP_056100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR7	ENST00000254442.8	c.3305-30795T>A		intron_variant	Intron 20 of 27	1	NM_015285.3	ENSP00000254442.3
WDR7	ENST00000357574.7	c.3206-30795T>A		intron_variant	Intron 19 of 26	5		ENSP00000350187.2
WDR7	ENST00000589935.1	c.1-177855T>A		intron_variant	Intron 1 of 1	4		ENSP00000467485.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43398 AN: 151888 Hom.: 7978 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.286 AC: 43446 AN: 152006 Hom.: 7990 Cov.: 32 AF XY: 0.284 AC XY: 21129 AN XY: 74288

African (AFR) AF: 0.528 AC: 21845 AN: 41404

American (AMR) AF: 0.207 AC: 3166 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3468

East Asian (EAS) AF: 0.0513 AC: 265 AN: 5168

South Asian (SAS) AF: 0.179 AC: 862 AN: 4812

European-Finnish (FIN) AF: 0.262 AC: 2769 AN: 10580

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12926 AN: 67988

Other (OTH) AF: 0.251 AC: 531 AN: 2114

Alfa AF: 0.249 Hom.: 748

Bravo AF: 0.295

Asia WGS AF: 0.125 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.70
PhyloP100		-0.72
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: rs2576415; hg19: chr18-54516380;