18-26576461-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000579973.5(KCTD1):​c.-16+52686C>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 ENST00000579973.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 16 publications found

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]

KCTD1 Gene-Disease associations (from GenCC):

• scalp-ear-nipple syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000579973.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD1	NM_001258222.3		c.10-75211C>A		intron	N/A	NP_001245151.1
	KCTD1	NM_198991.4		c.-16+52686C>A		intron	N/A	NP_945342.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD1	ENST00000579973.5	TSL:1	c.-16+52686C>A		intron	N/A	ENSP00000464170.1
	KCTD1	ENST00000580191.5	TSL:2	c.10-75211C>A		intron	N/A	ENSP00000464261.1
	KCTD1	ENST00000317932.11	TSL:5	c.-16+52686C>A		intron	N/A	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

African (AFR) AF: 0.0248 AC: 1029 AN: 41526

American (AMR) AF: 0.0911 AC: 1393 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.0857 AC: 443 AN: 5172

South Asian (SAS) AF: 0.0652 AC: 314 AN: 4814

European-Finnish (FIN) AF: 0.106 AC: 1124 AN: 10564

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5782 AN: 68010

Other (OTH) AF: 0.0881 AC: 186 AN: 2112

Alfa AF: 0.110 Hom.: 3825

Bravo AF: 0.0681

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.33
PhyloP100		-0.11
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: rs16942421; hg19: chr18-24156425;