rs16942421

Variant names:

• chr18-26576461-G-A
• rs16942421
• ENST00000579973.5:c.-16+52686C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-26576461-G-A
• chr18-26576461-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000579973.5(KCTD1):​c.-16+52686C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 152,194 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.021 (59 hom., cov: 33)
• Consequence: KCTD1 ENST00000579973.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• scalp-ear-nipple syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.021 (3189/152194) while in subpopulation NFE AF = 0.0326 (2219/68012). AF 95% confidence interval is 0.0315. There are 59 homozygotes in GnomAd4. There are 1514 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3189 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD1	NM_001258222.3	c.10-75211C>T		intron_variant	Intron 1 of 4		NP_001245151.1
KCTD1	NM_198991.4	c.-16+52686C>T		intron_variant	Intron 2 of 5		NP_945342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD1	ENST00000579973.5	c.-16+52686C>T		intron_variant	Intron 2 of 5	1		ENSP00000464170.1
KCTD1	ENST00000580191.5	c.10-75211C>T		intron_variant	Intron 1 of 4	2		ENSP00000464261.1
KCTD1	ENST00000317932.11	c.-16+52686C>T		intron_variant	Intron 1 of 4	5		ENSP00000314831.7

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3193 AN: 152076 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.00688

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0210 AC: 3189 AN: 152194 Hom.: 59 Cov.: 33 AF XY: 0.0204 AC XY: 1514 AN XY: 74394

African (AFR) AF: 0.00689 AC: 286 AN: 41526

American (AMR) AF: 0.0200 AC: 306 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4818

European-Finnish (FIN) AF: 0.00520 AC: 55 AN: 10568

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2219 AN: 68012

Other (OTH) AF: 0.0241 AC: 51 AN: 2114

Alfa AF: 0.0000860 Hom.: 3825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.84
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs16942421; hg19: chr18-24156425;