chr1-27269371-C-T

Variant names:

• chr1-27269371-C-T
• rs11589265
• NM_001276252.2:c.132+6136C>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.132+6136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 149,148 control chromosomes in the GnomAD database, including 3,536 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 0.19 (3536 hom., cov: 26)
• Consequence: WDTC1 NM_001276252.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDTC1	NM_001276252.2	c.132+6136C>T		intron_variant	Intron 3 of 15	ENST00000319394.8	NP_001263181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDTC1	ENST00000319394.8	c.132+6136C>T		intron_variant	Intron 3 of 15	1	NM_001276252.2	ENSP00000317971.3
WDTC1	ENST00000361771.7	c.132+6136C>T		intron_variant	Intron 3 of 15	1		ENSP00000355317.3
WDTC1	ENST00000447062.2	n.132+6136C>T		intron_variant	Intron 2 of 15	2		ENSP00000434578.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28072 AN: 149080 Hom.: 3537 Cov.: 26

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.188 AC: 28071 AN: 149148 Hom.: 3536 Cov.: 26 AF XY: 0.186 AC XY: 13510 AN XY: 72590

African (AFR) AF: 0.0528 AC: 2149 AN: 40710

American (AMR) AF: 0.164 AC: 2427 AN: 14838

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 763 AN: 3460

East Asian (EAS) AF: 0.0545 AC: 271 AN: 4972

South Asian (SAS) AF: 0.105 AC: 495 AN: 4710

European-Finnish (FIN) AF: 0.251 AC: 2451 AN: 9760

Middle Eastern (MID) AF: 0.128 AC: 37 AN: 290

European-Non Finnish (NFE) AF: 0.281 AC: 18937 AN: 67450

Other (OTH) AF: 0.179 AC: 367 AN: 2050

Alfa AF: 0.235 Hom.: 7790

Bravo AF: 0.174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.40
PhyloP100		0.028
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: rs11589265; hg19: chr1-27595862;