rs501415

chr18-56651611-A-Gchr18-56651611-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015285.3(WDR7):c.-20+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,210 control chromosomes in the GnomAD database, including 6,546 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 0.24 (6546 hom., cov: 33)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: WDR7 NM_015285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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]

TXNL1 (HGNC:12436): (thioredoxin like 1) Enables disulfide oxidoreductase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR7	NM_015285.3	c.-20+35A>G		intron_variant		ENST00000254442.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR7	ENST00000254442.8	c.-20+35A>G		intron_variant		1	NM_015285.3	P4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36015 AN: 151924 Hom.: 6525 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0388

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.120 AC: 20 AN: 166 Hom.: 0 Cov.: 0 AF XY: 0.138 AC XY: 18 AN XY: 130

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.0909

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.237 AC: 36082 AN: 152044 Hom.: 6546 Cov.: 33 AF XY: 0.230 AC XY: 17085 AN XY: 74334

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0391

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.193

Alfa AF: 0.187 Hom.: 488

Bravo AF: 0.255

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.5
Dann	Benign	0.20

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: rs501415; hg19: chr18-54318842;