chr18-26564147-C-T

Variant names:

• chr18-26564147-C-T
• rs10853666
• ENST00000579973.5:c.-15-62897G>A

Variant summary

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

The ENST00000579973.5(KCTD1):​c.-15-62897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,834 control chromosomes in the GnomAD database, including 9,245 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 0.33 (9245 hom., cov: 31)
• Consequence: KCTD1 ENST00000579973.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD1	NM_001258222.3	c.10-62897G>A		intron_variant	Intron 1 of 4		NP_001245151.1
KCTD1	NM_198991.4	c.-15-62897G>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.-15-62897G>A		intron_variant	Intron 2 of 5	1		ENSP00000464170.1
KCTD1	ENST00000580191.5	c.10-62897G>A		intron_variant	Intron 1 of 4	2		ENSP00000464261.1
KCTD1	ENST00000317932.11	c.-15-62897G>A		intron_variant	Intron 1 of 4	5		ENSP00000314831.7

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49797 AN: 151716 Hom.: 9240 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.328 AC: 49825 AN: 151834 Hom.: 9245 Cov.: 31 AF XY: 0.331 AC XY: 24531 AN XY: 74186

African (AFR) AF: 0.146 AC: 6054 AN: 41426

American (AMR) AF: 0.399 AC: 6085 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1358 AN: 3470

East Asian (EAS) AF: 0.583 AC: 2997 AN: 5140

South Asian (SAS) AF: 0.335 AC: 1608 AN: 4806

European-Finnish (FIN) AF: 0.387 AC: 4056 AN: 10482

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26313 AN: 67928

Other (OTH) AF: 0.368 AC: 775 AN: 2108

Alfa AF: 0.361 Hom.: 4665

Bravo AF: 0.325

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.71
PhyloP100		-0.22
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: rs10853666; hg19: chr18-24144111;