rs9946253

Variant names:

• chr18-56813248-A-C
• rs9946253
• NM_015285.3:c.3191-2783A>C

Your query was ambiguous. Multiple possible variants found:

• chr18-56813248-A-C
• chr18-56813248-A-G
• chr18-56813248-A-T

Variant summary

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

The NM_015285.3(WDR7):​c.3191-2783A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 151,296 control chromosomes in the GnomAD database, including 54,063 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 0.84 (54063 hom., cov: 27)
• Consequence: WDR7 NM_015285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 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.3191-2783A>C		intron	N/A	NP_056100.2
	WDR7	NM_001382487.1		c.3191-2783A>C		intron	N/A	NP_001369416.1
	WDR7	NM_001382485.1		c.3092-2783A>C		intron	N/A	NP_001369414.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR7	ENST00000254442.8	TSL:1 MANE Select	c.3191-2783A>C		intron	N/A	ENSP00000254442.3
	WDR7	ENST00000357574.7	TSL:5	c.3092-2783A>C		intron	N/A	ENSP00000350187.2
	WDR7	ENST00000589935.1	TSL:4	c.-1+161672A>C		intron	N/A	ENSP00000467485.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 127608 AN: 151180 Hom.: 54016 Cov.: 27

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.901

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.844 AC: 127716 AN: 151296 Hom.: 54063 Cov.: 27 AF XY: 0.844 AC XY: 62295 AN XY: 73850

African (AFR) AF: 0.788 AC: 32469 AN: 41230

American (AMR) AF: 0.870 AC: 13208 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3168 AN: 3466

East Asian (EAS) AF: 0.985 AC: 5061 AN: 5136

South Asian (SAS) AF: 0.878 AC: 4195 AN: 4778

European-Finnish (FIN) AF: 0.785 AC: 8158 AN: 10386

Middle Eastern (MID) AF: 0.897 AC: 260 AN: 290

European-Non Finnish (NFE) AF: 0.865 AC: 58655 AN: 67806

Other (OTH) AF: 0.866 AC: 1823 AN: 2104

Alfa AF: 0.862 Hom.: 28201

Bravo AF: 0.847

Asia WGS AF: 0.934 AC: 3248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.65
PhyloP100		-1.0
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: rs9946253; hg19: chr18-54480479;