chr4-10088139-C-T

Variant names:

• chr4-10088139-C-T
• rs2241480
• NM_017491.5:c.717+154G>A

Variant summary

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

The NM_017491.5(WDR1):​c.717+154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 900,388 control chromosomes in the GnomAD database, including 44,245 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 0.30 (7187 hom., cov: 32)
  • Exomes 𝑓: 0.31 (37058 hom.)
• Consequence: WDR1 NM_017491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017491.5. 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
	WDR1	NM_017491.5	MANE Select	c.717+154G>A		intron	N/A	NP_059830.1	O75083-1
	WDR1	NM_005112.5		c.297+154G>A		intron	N/A	NP_005103.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR1	ENST00000499869.7	TSL:5 MANE Select	c.717+154G>A		intron	N/A	ENSP00000427687.1	O75083-1
	WDR1	ENST00000699794.1		c.876+154G>A		intron	N/A	ENSP00000514596.1	A0A8V8TP22
	WDR1	ENST00000867002.1		c.717+154G>A		intron	N/A	ENSP00000537061.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45357 AN: 151924 Hom.: 7167 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.308 AC: 230734 AN: 748346 Hom.: 37058 AF XY: 0.308 AC XY: 118954 AN XY: 385892

African (AFR) AF: 0.242 AC: 4540 AN: 18770

American (AMR) AF: 0.356 AC: 11080 AN: 31164

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 7672 AN: 18390

East Asian (EAS) AF: 0.527 AC: 17220 AN: 32682

South Asian (SAS) AF: 0.301 AC: 17950 AN: 59648

European-Finnish (FIN) AF: 0.307 AC: 12791 AN: 41678

Middle Eastern (MID) AF: 0.354 AC: 973 AN: 2752

European-Non Finnish (NFE) AF: 0.290 AC: 146802 AN: 507044

Other (OTH) AF: 0.323 AC: 11706 AN: 36218

GnomAD4 genome AF: 0.299 AC: 45409 AN: 152042 Hom.: 7187 Cov.: 32 AF XY: 0.301 AC XY: 22399 AN XY: 74320

African (AFR) AF: 0.243 AC: 10082 AN: 41488

American (AMR) AF: 0.358 AC: 5472 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3468

East Asian (EAS) AF: 0.535 AC: 2759 AN: 5154

South Asian (SAS) AF: 0.308 AC: 1484 AN: 4814

European-Finnish (FIN) AF: 0.290 AC: 3060 AN: 10566

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19801 AN: 67958

Other (OTH) AF: 0.325 AC: 684 AN: 2106

Alfa AF: 0.274 Hom.: 3354

Bravo AF: 0.305

Asia WGS AF: 0.410 AC: 1421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.62
PhyloP100		-0.83
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: rs2241480; hg19: chr4-10089763;