18-26459525-A-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.2439+95T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 1,223,688 control chromosomes in the GnomAD database, including 528,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (64216 hom., cov: 33)
  • Exomes 𝑓: 0.93 (464618 hom.)
• Consequence: KCTD1 NM_001142730.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.651

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=-0.9).
• BP6: Variant 18-26459525-A-C is Benign according to our data. Variant chr18-26459525-A-C is described in ClinVar as [Benign]. Clinvar id is 1282752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD1	NM_001142730.3	c.2439+95T>G		intron_variant		ENST00000580059.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD1	ENST00000580059.7	c.2439+95T>G		intron_variant		3	NM_001142730.3	P1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139687 AN: 152186 Hom.: 64169 Cov.: 33

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.930

GnomAD4 exome AF: 0.931 AC: 997438 AN: 1071384 Hom.: 464618 Cov.: 14 AF XY: 0.930 AC XY: 496401 AN XY: 533978

Gnomad4 AFR exome AF: 0.886

Gnomad4 AMR exome AF: 0.965

Gnomad4 ASJ exome AF: 0.955

Gnomad4 EAS exome AF: 0.962

Gnomad4 SAS exome AF: 0.904

Gnomad4 FIN exome AF: 0.897

Gnomad4 NFE exome AF: 0.933

Gnomad4 OTH exome AF: 0.931

GnomAD4 genome AF: 0.918 AC: 139795 AN: 152304 Hom.: 64216 Cov.: 33 AF XY: 0.917 AC XY: 68308 AN XY: 74468

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.930

Alfa AF: 0.931 Hom.: 89437

Bravo AF: 0.922

Asia WGS AF: 0.925 AC: 3218 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.4
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752856; hg19: chr18-24039489;