18-26455981-A-G

Position:

• chr18-26455981-A-G

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.2440-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 1,377,624 control chromosomes in the GnomAD database, including 2,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (301 hom., cov: 32)
  • Exomes 𝑓: 0.052 (1746 hom.)
• Consequence: KCTD1 NM_001142730.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.599

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=-0.82).
• BP6: Variant 18-26455981-A-G is Benign according to our data. Variant chr18-26455981-A-G is described in ClinVar as [Benign]. Clinvar id is 1232468.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD1	NM_001142730.3	c.2440-80T>C		intron_variant		ENST00000580059.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD1	ENST00000580059.7	c.2440-80T>C		intron_variant		3	NM_001142730.3	P1

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8463 AN: 152146 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0662

GnomAD4 exome AF: 0.0522 AC: 63993 AN: 1225360 Hom.: 1746 Cov.: 16 AF XY: 0.0511 AC XY: 31080 AN XY: 607672

Gnomad4 AFR exome AF: 0.0782

Gnomad4 AMR exome AF: 0.0300

Gnomad4 ASJ exome AF: 0.0682

Gnomad4 EAS exome AF: 0.0441

Gnomad4 SAS exome AF: 0.0168

Gnomad4 FIN exome AF: 0.0653

Gnomad4 NFE exome AF: 0.0541

Gnomad4 OTH exome AF: 0.0524

GnomAD4 genome AF: 0.0557 AC: 8479 AN: 152264 Hom.: 301 Cov.: 32 AF XY: 0.0564 AC XY: 4200 AN XY: 74438

Gnomad4 AFR AF: 0.0753

Gnomad4 AMR AF: 0.0317

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.0525

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0646

Gnomad4 NFE AF: 0.0503

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0580 Hom.: 59

Bravo AF: 0.0561

Asia WGS AF: 0.0650 AC: 226 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 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.63

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: rs12956508; hg19: chr18-24035945;