4-10113899-A-G

Variant names:

• chr4-10113899-A-G
• rs12498927
• NM_017491.5:c.138+2214T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017491.5(WDR1):​c.138+2214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,008 control chromosomes in the GnomAD database, including 20,283 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 0.51 (20283 hom., cov: 33)
• Consequence: WDR1 NM_017491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR1	NM_017491.5	c.138+2214T>C		intron_variant	Intron 2 of 14	ENST00000499869.7	NP_059830.1
WDR1	NM_005112.5	c.138+2214T>C		intron_variant	Intron 2 of 11		NP_005103.2
WDR1	XM_017008880.3	c.138+2214T>C		intron_variant	Intron 2 of 14		XP_016864369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR1	ENST00000499869.7	c.138+2214T>C		intron_variant	Intron 2 of 14	5	NM_017491.5	ENSP00000427687.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78126 AN: 151890 Hom.: 20249 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.514 AC: 78206 AN: 152008 Hom.: 20283 Cov.: 33 AF XY: 0.513 AC XY: 38091 AN XY: 74296

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.537

Alfa AF: 0.501 Hom.: 4033

Bravo AF: 0.517

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs12498927; hg19: chr4-10115523;