18-26576461-G-T

Variant names:

• chr18-26576461-G-T
• rs16942421
• ENST00000579973.5:c.-16+52686C>A

Variant summary

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

The NM_001258222.3(KCTD1):​c.10-75211C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 152,170 control chromosomes in the GnomAD database, including 405 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 0.069 (405 hom., cov: 33)
• Consequence: KCTD1 NM_001258222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD1	NM_001258222.3	c.10-75211C>A		intron_variant	Intron 1 of 4		NP_001245151.1
KCTD1	NM_198991.4	c.-16+52686C>A		intron_variant	Intron 2 of 5		NP_945342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD1	ENST00000579973.5	c.-16+52686C>A		intron_variant	Intron 2 of 5	1		ENSP00000464170.1
KCTD1	ENST00000580191.5	c.10-75211C>A		intron_variant	Intron 1 of 4	2		ENSP00000464261.1
KCTD1	ENST00000317932.11	c.-16+52686C>A		intron_variant	Intron 1 of 4	5		ENSP00000314831.7

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10487 AN: 152052 Hom.: 399 Cov.: 33

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.0858

Gnomad SAS AF: 0.0641

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0691 AC: 10515 AN: 152170 Hom.: 405 Cov.: 33 AF XY: 0.0707 AC XY: 5256 AN XY: 74384

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.0911

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.0857

Gnomad4 SAS AF: 0.0652

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0850

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.110 Hom.: 1917

Bravo AF: 0.0681

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.33

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: rs16942421; hg19: chr18-24156425;