rs284856

chr10-102814572-A-T

Variant summary

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

The NM_001083913.2(WBP1L):c.*1241A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 148,536 control chromosomes in the GnomAD database, including 24,158 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 0.57 (24079 hom., cov: 23)
  • Exomes 𝑓: 0.58 (79 hom.)
• Consequence: WBP1L NM_001083913.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

Genes affected

WBP1L (HGNC:23510): (WW domain binding protein 1 like) Predicted to enable ubiquitin protein ligase binding activity. Predicted to act upstream of or within CXCL12-activated CXCR4 signaling pathway; hemopoiesis; and positive regulation of protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WBP1L	NM_001083913.2	c.*1241A>T		3_prime_UTR_variant	4/4	ENST00000448841.7
WBP1L	NM_017787.5	c.*1241A>T		3_prime_UTR_variant	4/4
WBP1L	XM_011539913.3	c.*1241A>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP1L	ENST00000448841.7	c.*1241A>T		3_prime_UTR_variant	4/4	2	NM_001083913.2	A2
WBP1L	ENST00000369889.5	c.*1241A>T		3_prime_UTR_variant	4/4	1		P4
WBP1L	ENST00000647664.1	c.355+4518A>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.569 AC: 84278 AN: 147998 Hom.: 24060 Cov.: 23

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.587

GnomAD4 exome AF: 0.584 AC: 250 AN: 428 Hom.: 79 Cov.: 0 AF XY: 0.605 AC XY: 155 AN XY: 256

Gnomad4 FIN exome AF: 0.585

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.569 AC: 84342 AN: 148108 Hom.: 24079 Cov.: 23 AF XY: 0.573 AC XY: 41197 AN XY: 71884

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.585

Alfa AF: 0.561 Hom.: 3004

Bravo AF: 0.563

Asia WGS AF: 0.572 AC: 1991 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	9.1
Dann	Benign	0.83

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: rs284856; hg19: chr10-104574329; COSMIC: COSV64009638;