Variant 18-26455824-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142730.3(KCTD1):c.2517C>T(p.Ser839=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,613,940 control chromosomes in the GnomAD database, including 19,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1609 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17752 hom. )

Consequence

KCTD1
NM_001142730.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0920

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 18-26455824-G-A is Benign according to our data. Variant chr18-26455824-G-A is described in ClinVar as [Benign]. Clinvar id is 1243729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.092 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD1	NM_001142730.3 linkuse as main transcript	c.2517C>T	p.Ser839=	synonymous_variant	5/5	ENST00000580059.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD1	ENST00000580059.7 linkuse as main transcript	c.2517C>T	p.Ser839=	synonymous_variant	5/5	3	NM_001142730.3	P1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20593

AN:

152064

Hom.:

1609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0455

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.123

AC:

30952

AN:

251404

Hom.:

2485

AF XY:

0.122

AC XY:

16611

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.0697

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.00245

Gnomad SAS exome

AF:

0.0451

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.148

AC:

216894

AN:

1461758

Hom.:

17752

Cov.:

AF XY:

0.146

AC XY:

106083

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0738

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.00433

Gnomad4 SAS exome

AF:

0.0477

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.135

AC:

20596

AN:

152182

Hom.:

1609

Cov.:

AF XY:

0.134

AC XY:

9970

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.00308

Gnomad4 SAS

AF:

0.0453

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.147

Hom.:

3205

Bravo

AF:

0.124

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.155

EpiControl

AF:

0.154

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

KCTD1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

Cadd

Benign

7.8

Dann

Benign

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over