18-26564147-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001258222.3(KCTD1):​c.10-62897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,834 control chromosomes in the GnomAD database, including 9,245 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 0.33 ( 9245 hom., cov: 31)

Consequence

KCTD1
NM_001258222.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.217
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCTD1NM_001258222.3 linkc.10-62897G>A intron_variant Intron 1 of 4 NP_001245151.1
KCTD1NM_198991.4 linkc.-15-62897G>A intron_variant Intron 2 of 5 NP_945342.1 Q719H9A0A024RC45

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCTD1ENST00000579973.5 linkc.-15-62897G>A intron_variant Intron 2 of 5 1 ENSP00000464170.1 Q719H9
KCTD1ENST00000580191.5 linkc.10-62897G>A intron_variant Intron 1 of 4 2 ENSP00000464261.1 J3QRK1
KCTD1ENST00000317932.11 linkc.-15-62897G>A intron_variant Intron 1 of 4 5 ENSP00000314831.7 Q719H9

Frequencies

GnomAD3 genomes
AF:
0.328
AC:
49797
AN:
151716
Hom.:
9240
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.146
Gnomad AMI
AF:
0.503
Gnomad AMR
AF:
0.398
Gnomad ASJ
AF:
0.391
Gnomad EAS
AF:
0.583
Gnomad SAS
AF:
0.334
Gnomad FIN
AF:
0.387
Gnomad MID
AF:
0.402
Gnomad NFE
AF:
0.387
Gnomad OTH
AF:
0.365
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.328
AC:
49825
AN:
151834
Hom.:
9245
Cov.:
31
AF XY:
0.331
AC XY:
24531
AN XY:
74186
show subpopulations
Gnomad4 AFR
AF:
0.146
Gnomad4 AMR
AF:
0.399
Gnomad4 ASJ
AF:
0.391
Gnomad4 EAS
AF:
0.583
Gnomad4 SAS
AF:
0.335
Gnomad4 FIN
AF:
0.387
Gnomad4 NFE
AF:
0.387
Gnomad4 OTH
AF:
0.368
Alfa
AF:
0.366
Hom.:
3908
Bravo
AF:
0.325
Asia WGS
AF:
0.444
AC:
1544
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.4
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs10853666; hg19: chr18-24144111; API