NM_015285.3:c.-20+35A>G

Variant names:

• chr18-56651611-A-G
• rs501415
• NM_015285.3:c.-20+35A>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.-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
• Publications: 6 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015285.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR7	NM_015285.3	MANE Select	c.-20+35A>G		intron	N/A	NP_056100.2
	WDR7	NM_052834.3		c.-20+35A>G		intron	N/A	NP_443066.2
	WDR7	NM_001382487.1		c.-207A>G		upstream_gene	N/A	NP_001369416.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR7	ENST00000254442.8	TSL:1 MANE Select	c.-20+35A>G		intron	N/A	ENSP00000254442.3
	WDR7	ENST00000357574.7	TSL:5	c.-20+35A>G		intron	N/A	ENSP00000350187.2
	WDR7	ENST00000589935.1	TSL:4	c.-1+35A>G		intron	N/A	ENSP00000467485.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.167 AC: 1 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0909 AC: 2 AN: 22

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.121 AC: 15 AN: 124

Other (OTH) AF: 0.100 AC: 1 AN: 10

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

African (AFR) AF: 0.522 AC: 21588 AN: 41366

American (AMR) AF: 0.133 AC: 2027 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3472

East Asian (EAS) AF: 0.0391 AC: 202 AN: 5172

South Asian (SAS) AF: 0.0988 AC: 477 AN: 4828

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10608

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9413 AN: 67990

Other (OTH) AF: 0.193 AC: 407 AN: 2108

Alfa AF: 0.169 Hom.: 4647

Bravo AF: 0.255

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.20
PhyloP100		-1.6
PromoterAI		0.035	Neutral
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: rs501415; hg19: chr18-54318842;