rs9948310

Variant names:

• chr18-26556290-T-C
• rs9948310
• ENST00000579973.5:c.-15-55040A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-26556290-T-C
• chr18-26556290-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000579973.5(KCTD1):​c.-15-55040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,164 control chromosomes in the GnomAD database, including 1,653 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 0.14 (1653 hom., cov: 32)
• Consequence: KCTD1 ENST00000579973.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 8 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)

ENSG00000308088 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD1	NM_001258222.3	c.10-55040A>G		intron_variant	Intron 1 of 4		NP_001245151.1
KCTD1	NM_198991.4	c.-15-55040A>G		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.-15-55040A>G		intron_variant	Intron 2 of 5	1		ENSP00000464170.1
KCTD1	ENST00000580191.5	c.10-55040A>G		intron_variant	Intron 1 of 4	2		ENSP00000464261.1
KCTD1	ENST00000317932.11	c.-15-55040A>G		intron_variant	Intron 1 of 4	5		ENSP00000314831.7
ENSG00000308088	ENST00000831012.1	n.*247T>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21577 AN: 152046 Hom.: 1653 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.142 AC: 21580 AN: 152164 Hom.: 1653 Cov.: 32 AF XY: 0.145 AC XY: 10752 AN XY: 74386

African (AFR) AF: 0.0995 AC: 4130 AN: 41520

American (AMR) AF: 0.193 AC: 2947 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3466

East Asian (EAS) AF: 0.136 AC: 707 AN: 5180

South Asian (SAS) AF: 0.186 AC: 898 AN: 4822

European-Finnish (FIN) AF: 0.181 AC: 1917 AN: 10576

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10077 AN: 67996

Other (OTH) AF: 0.143 AC: 302 AN: 2114

Alfa AF: 0.143 Hom.: 3297

Bravo AF: 0.143

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.3
DANN	Benign	0.88
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs9948310; hg19: chr18-24136254;