4-10103046-A-G

Variant names:

• chr4-10103046-A-G
• rs717615
• NM_017491.5:c.229+850T>C

Variant summary

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

The NM_017491.5(WDR1):​c.229+850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,964 control chromosomes in the GnomAD database, including 15,657 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 0.45 (15657 hom., cov: 31)
• Consequence: WDR1 NM_017491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 35 publications found

Genes affected

WDR1 (HGNC:12754): (WD repeat domain 1) This gene encodes a protein containing 9 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, mostly including a trp-asp at the C-terminal end. WD domains are involved in protein-protein interactions. The encoded protein may help induce the disassembly of actin filaments. Two transcript variants encoding different isoforms have been found for this gene. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR1	NM_017491.5	c.229+850T>C		intron_variant	Intron 3 of 14	ENST00000499869.7	NP_059830.1
WDR1	NM_005112.5	c.138+13067T>C		intron_variant	Intron 2 of 11		NP_005103.2
WDR1	XM_017008880.3	c.229+850T>C		intron_variant	Intron 3 of 14		XP_016864369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR1	ENST00000499869.7	c.229+850T>C		intron_variant	Intron 3 of 14	5	NM_017491.5	ENSP00000427687.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67988 AN: 151846 Hom.: 15646 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.448 AC: 68029 AN: 151964 Hom.: 15657 Cov.: 31 AF XY: 0.449 AC XY: 33380 AN XY: 74284

African (AFR) AF: 0.337 AC: 13949 AN: 41432

American (AMR) AF: 0.544 AC: 8303 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1641 AN: 3464

East Asian (EAS) AF: 0.503 AC: 2598 AN: 5162

South Asian (SAS) AF: 0.404 AC: 1946 AN: 4818

European-Finnish (FIN) AF: 0.479 AC: 5062 AN: 10566

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32952 AN: 67944

Other (OTH) AF: 0.459 AC: 965 AN: 2104

Alfa AF: 0.471 Hom.: 60211

Bravo AF: 0.446

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.68
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs717615; hg19: chr4-10104670;