chr18-57029383-C-G

Position:

• chr18-57029383-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015285.3(WDR7):​c.*2176C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 152,286 control chromosomes in the GnomAD database, including 36 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 0.020 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR7 NM_015285.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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-OT1 (HGNC:45131): (WDR7 overlapping transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0199 (3037/152286) while in subpopulation EAS AF= 0.0499 (258/5172). AF 95% confidence interval is 0.0449. There are 36 homozygotes in gnomad4. There are 1423 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3037 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR7	NM_015285.3	c.*2176C>G		3_prime_UTR_variant	28/28	ENST00000254442.8	NP_056100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR7	ENST00000254442.8	c.*2176C>G		3_prime_UTR_variant	28/28	1	NM_015285.3	ENSP00000254442	P4
WDR7-OT1	ENST00000592032.1	n.390-442C>G		intron_variant, non_coding_transcript_variant		4
WDR7	ENST00000357574.7	c.*2176C>G		3_prime_UTR_variant	27/27	5		ENSP00000350187	A1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3035 AN: 152168 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00642

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0496

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0143

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0199 AC: 3037 AN: 152286 Hom.: 36 Cov.: 32 AF XY: 0.0191 AC XY: 1423 AN XY: 74466

Gnomad4 AFR AF: 0.00640

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.0499

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.00989

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0190 Hom.: 4

Bravo AF: 0.0200

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.52

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: rs3745030; hg19: chr18-54696614;