chr1-27257502-C-T

Variant names:

• chr1-27257502-C-T
• rs4460661
• NM_001276252.2:c.-99-3454C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WDTC1	NM_001276252.2	c.-99-3454C>T		intron_variant	Intron 1 of 15	ENST00000319394.8	NP_001263181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDTC1	ENST00000319394.8	c.-99-3454C>T		intron_variant	Intron 1 of 15	1	NM_001276252.2	ENSP00000317971.3
WDTC1	ENST00000361771.7	c.-99-3454C>T		intron_variant	Intron 1 of 15	1		ENSP00000355317.3

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

African (AFR) AF: 0.635 AC: 26313 AN: 41466

American (AMR) AF: 0.875 AC: 13361 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3089 AN: 3470

East Asian (EAS) AF: 0.883 AC: 4559 AN: 5166

South Asian (SAS) AF: 0.815 AC: 3933 AN: 4826

European-Finnish (FIN) AF: 0.791 AC: 8367 AN: 10572

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58140 AN: 68002

Other (OTH) AF: 0.829 AC: 1750 AN: 2110

Alfa AF: 0.842 Hom.: 47236

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
PhyloP100		-0.24
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: rs4460661; hg19: chr1-27583993;