rs17750015

Positions:

• chr18-56730391-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

WDR7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR7	NM_015285.3	c.1775-992T>C		intron_variant		ENST00000254442.8	NP_056100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR7	ENST00000254442.8	c.1775-992T>C		intron_variant		1	NM_015285.3	ENSP00000254442.3

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

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.321

Alfa AF: 0.350 Hom.: 16872

Bravo AF: 0.274

Asia WGS AF: 0.294 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.71

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: rs17750015; hg19: chr18-54397622;