1-27257502-C-T

Position:

• chr1-27257502-C-T

Variant summary

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

The NM_001276252.2(WDTC1):​c.-99-3454C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,094 control chromosomes in the GnomAD database, including 48,629 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 0.79 (48629 hom., cov: 32)
• Consequence: WDTC1 NM_001276252.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

Genes affected

WDTC1 (HGNC:29175): (WD and tetratricopeptide repeats 1) Predicted to enable enzyme inhibitor activity; histone binding activity; and histone deacetylase binding activity. Predicted to be involved in negative regulation of fatty acid biosynthetic process. Predicted to act upstream of or within several processes, including cellular response to insulin stimulus; glucose metabolic process; and negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of Cul4-RING E3 ubiquitin ligase complex. Predicted to be active in cytoplasm. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDTC1	NM_001276252.2	c.-99-3454C>T		intron_variant		ENST00000319394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDTC1	ENST00000319394.8	c.-99-3454C>T		intron_variant		1	NM_001276252.2	P5
WDTC1	ENST00000361771.7	c.-99-3454C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120482 AN: 151976 Hom.: 48593 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.793 AC: 120569 AN: 152094 Hom.: 48629 Cov.: 32 AF XY: 0.791 AC XY: 58830 AN XY: 74334

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.829

Alfa AF: 0.845 Hom.: 40270

Bravo AF: 0.793

Asia WGS AF: 0.824 AC: 2865 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	1.5
DANN	Benign	0.37

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: rs4460661; hg19: chr1-27583993;