chr18-26479292-A-G

Position:

• chr18-26479292-A-G

Variant summary

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

The NM_001142730.3(KCTD1):​c.1989-2633T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,956 control chromosomes in the GnomAD database, including 41,961 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 0.74 (41961 hom., cov: 30)
• Consequence: KCTD1 NM_001142730.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

KCTD1 (HGNC:18249): (potassium channel tetramerization domain containing 1) This gene encodes a protein containing a BTB (Broad-complex, tramtrack and bric a brac), also known as a POZ (POxvirus and zinc finger) protein-protein interaction domain. The encoded protein negatively regulates the AP-2 family of transcription factors and the Wnt signaling pathway. A mechanism for the modulation of Wnt signaling has been proposed in which the encoded protein enhances ubiquitination and degradation of the beta-catenin protein. Mutations in this gene have been identified in Scalp-ear-nipple (SEN) syndrome. [provided by RefSeq, May 2017]

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 = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD1	NM_001142730.3	c.1989-2633T>C		intron_variant		ENST00000580059.7	NP_001136202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD1	ENST00000580059.7	c.1989-2633T>C		intron_variant		3	NM_001142730.3	ENSP00000463041.2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111873 AN: 151838 Hom.: 41956 Cov.: 30

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.737 AC: 111916 AN: 151956 Hom.: 41961 Cov.: 30 AF XY: 0.733 AC XY: 54465 AN XY: 74254

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.767

Alfa AF: 0.790 Hom.: 67790

Bravo AF: 0.740

Asia WGS AF: 0.895 AC: 3113 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	0.67
DANN	Benign	0.78

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: rs6508445; hg19: chr18-24059256;