rs6566846

Variant names:

• chr18-56932876-T-G
• rs6566846
• NM_015285.3:c.3714-2912T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015285.3(WDR7):​c.3714-2912T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00067 (0 hom., cov: 0)
• Consequence: WDR7 NM_015285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High AC in GnomAd4 at 20 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR7	NM_015285.3	MANE Select	c.3714-2912T>G		intron	N/A	NP_056100.2	Q9Y4E6-1
	WDR7	NM_001382487.1		c.3714-2912T>G		intron	N/A	NP_001369416.1	Q9Y4E6-1
	WDR7	NM_001382485.1		c.3615-2912T>G		intron	N/A	NP_001369414.1	Q9Y4E6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR7	ENST00000254442.8	TSL:1 MANE Select	c.3714-2912T>G		intron	N/A	ENSP00000254442.3	Q9Y4E6-1
	WDR7	ENST00000357574.7	TSL:5	c.3615-2912T>G		intron	N/A	ENSP00000350187.2	Q9Y4E6-2
	WDR7	ENST00000589935.1	TSL:4	c.1-94128T>G		intron	N/A	ENSP00000467485.1	K7EPQ4

Frequencies

GnomAD3 genomes AF: 0.000671 AC: 20 AN: 29808 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000919

Gnomad FIN AF: 0.000399

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000777

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000671 AC: 20 AN: 29806 Hom.: 0 Cov.: 0 AF XY: 0.000483 AC XY: 7 AN XY: 14494

African (AFR) AF: 0.00101 AC: 6 AN: 5926

American (AMR) AF: 0.00 AC: 0 AN: 3212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 606

East Asian (EAS) AF: 0.00 AC: 0 AN: 382

South Asian (SAS) AF: 0.000919 AC: 1 AN: 1088

European-Finnish (FIN) AF: 0.000399 AC: 1 AN: 2506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.000777 AC: 12 AN: 15438

Other (OTH) AF: 0.00 AC: 0 AN: 436

Alfa AF: 0.158 Hom.: 1219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.52
PhyloP100		-0.098

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6566846;

hg19: chr18-54600107;