18-26455940-GTAAGTCC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001142730.3(KCTD1):c.2440-46_2440-40del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 1,599,592 control chromosomes in the GnomAD database, including 2,113 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (257 hom., cov: 31)
  • Exomes 𝑓: 0.049 (1856 hom.)
• Consequence: KCTD1 NM_001142730.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.802

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 -10 ACMG points.

• BP6: Variant 18-26455940-GTAAGTCC-G is Benign according to our data. Variant chr18-26455940-GTAAGTCC-G is described in ClinVar as [Benign]. Clinvar id is 1232178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD1	NM_001142730.3	c.2440-46_2440-40del		intron_variant		ENST00000580059.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD1	ENST00000580059.7	c.2440-46_2440-40del		intron_variant		3	NM_001142730.3	P1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8100 AN: 152144 Hom.: 256 Cov.: 31

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0638

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0502

Gnomad OTH AF: 0.0626

GnomAD3 exomes AF: 0.0459 AC: 11081 AN: 241270 Hom.: 290 AF XY: 0.0447 AC XY: 5838 AN XY: 130598

Gnomad AFR exome AF: 0.0672

Gnomad AMR exome AF: 0.0248

Gnomad ASJ exome AF: 0.0686

Gnomad EAS exome AF: 0.0492

Gnomad SAS exome AF: 0.0127

Gnomad FIN exome AF: 0.0636

Gnomad NFE exome AF: 0.0518

Gnomad OTH exome AF: 0.0545

GnomAD4 exome AF: 0.0489 AC: 70725 AN: 1447330 Hom.: 1856 AF XY: 0.0479 AC XY: 34385 AN XY: 718232

Gnomad4 AFR exome AF: 0.0668

Gnomad4 AMR exome AF: 0.0270

Gnomad4 ASJ exome AF: 0.0658

Gnomad4 EAS exome AF: 0.0435

Gnomad4 SAS exome AF: 0.0131

Gnomad4 FIN exome AF: 0.0634

Gnomad4 NFE exome AF: 0.0511

Gnomad4 OTH exome AF: 0.0485

GnomAD4 genome AF: 0.0532 AC: 8104 AN: 152262 Hom.: 257 Cov.: 31 AF XY: 0.0537 AC XY: 4001 AN XY: 74442

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.0520

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0638

Gnomad4 NFE AF: 0.0502

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0549 Hom.: 49

Bravo AF: 0.0536

Asia WGS AF: 0.0600 AC: 208 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

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71376961; hg19: chr18-24035904;