dbSNP rs12956508: KCTD1:c.2440-80T>C (chr18-26455981-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142730.3(KCTD1):c.2440-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 1,377,624 control chromosomes in the GnomAD database, including 2,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 301 hom., cov: 32)

Exomes 𝑓: 0.052 ( 1746 hom. )

Consequence

KCTD1
NM_001142730.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.599

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]

KCTD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 18-26455981-A-G is Benign according to our data. Variant chr18-26455981-A-G is described in ClinVar as [Benign]. Clinvar id is 1232468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD1	NM_001142730.3 link	c.2440-80T>C		intron_variant	Intron 4 of 4	ENST00000580059.7	NP_001136202.1	Q719H9A0A2U3U043

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD1	ENST00000580059.7 link	c.2440-80T>C		intron_variant	Intron 4 of 4	3	NM_001142730.3	ENSP00000463041.2		A0A2U3U043

Frequencies

GnomAD3 genomes

AF:

0.0556

AC:

8463

AN:

152146

Hom.:

295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0751

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.0526

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.0646

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0503

Gnomad OTH

AF:

0.0662

GnomAD4 exome

AF:

0.0522

AC:

63993

AN:

1225360

Hom.:

1746

Cov.:

AF XY:

0.0511

AC XY:

31080

AN XY:

607672

show subpopulations

African (AFR)

AF:

0.0782

AC:

2184

AN:

27944

American (AMR)

AF:

0.0300

AC:

897

AN:

29882

Ashkenazi Jewish (ASJ)

AF:

0.0682

AC:

1408

AN:

20638

East Asian (EAS)

AF:

0.0441

AC:

1614

AN:

36624

South Asian (SAS)

AF:

0.0168

AC:

1179

AN:

70014

European-Finnish (FIN)

AF:

0.0653

AC:

3025

AN:

46328

Middle Eastern (MID)

AF:

0.0546

AC:

274

AN:

5020

European-Non Finnish (NFE)

AF:

0.0541

AC:

50699

AN:

937138

Other (OTH)

AF:

0.0524

AC:

2713

AN:

51772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

2910

5820

8729

11639

14549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0557

AC:

8479

AN:

152264

Hom.:

301

Cov.:

AF XY:

0.0564

AC XY:

4200

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0753

AC:

3128

AN:

41554

American (AMR)

AF:

0.0317

AC:

485

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

230

AN:

3468

East Asian (EAS)

AF:

0.0525

AC:

272

AN:

5180

South Asian (SAS)

AF:

0.0174

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0646

AC:

684

AN:

10594

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0503

AC:

3424

AN:

68022

Other (OTH)

AF:

0.0678

AC:

143

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

401

802

1202

1603

2004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0580

Hom.:

Bravo

AF:

0.0561

Asia WGS

AF:

0.0650

AC:

226

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 16, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.1

(source)

DANN

Benign

0.63

PhyloP100

0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs12956508

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over