18-26455711-T-C

Position:

• chr18-26455711-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001142730.3(KCTD1):​c.*32A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,082 control chromosomes in the GnomAD database, including 13,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2054 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11197 hom.)
• Consequence: KCTD1 NM_001142730.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.203

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 18-26455711-T-C is Benign according to our data. Variant chr18-26455711-T-C is described in ClinVar as [Benign]. Clinvar id is 1245415.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD1	NM_001142730.3	c.*32A>G		3_prime_UTR_variant	5/5	ENST00000580059.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD1	ENST00000580059.7	c.*32A>G		3_prime_UTR_variant	5/5	3	NM_001142730.3	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23150 AN: 151982 Hom.: 2054 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.135 AC: 33825 AN: 251082 Hom.: 2755 AF XY: 0.131 AC XY: 17713 AN XY: 135712

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.0629

Gnomad EAS exome AF: 0.0455

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.117 AC: 171198 AN: 1460982 Hom.: 11197 Cov.: 32 AF XY: 0.117 AC XY: 85401 AN XY: 726822

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.0646

Gnomad4 EAS exome AF: 0.0472

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.152 AC: 23181 AN: 152100 Hom.: 2054 Cov.: 32 AF XY: 0.154 AC XY: 11470 AN XY: 74378

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.0536

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.128

Alfa AF: 0.119 Hom.: 342

Bravo AF: 0.156

Asia WGS AF: 0.128 AC: 443 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.62

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: rs3753; hg19: chr18-24035675; COSMIC: COSV58691154; COSMIC: COSV58691154;