dbSNP rs483731: KCTD21:c.-29-3115G>A (chr11-78177698-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001029859.3(KCTD21):c.-29-3115G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,316 control chromosomes in the GnomAD database, including 1,362 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 0.13 ( 1362 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

KCTD21
NM_001029859.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.383

Publications

1 publications found

Variant links:

Genes affected

KCTD21 (HGNC:27452): (potassium channel tetramerization domain containing 21) Enables cullin family protein binding activity; histone deacetylase binding activity; and identical protein binding activity. Involved in negative regulation of smoothened signaling pathway and ubiquitin-dependent protein catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

KCTD21 links:

KCTD21-AS1 (HGNC:48674): (KCTD21 antisense RNA 1)

KCTD21-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029859.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD21	NM_001029859.3	MANE Select	c.-29-3115G>A		intron	N/A	NP_001025030.1	Q4G0X4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCTD21	ENST00000340067.4	TSL:1 MANE Select	c.-29-3115G>A	intron	N/A	ENSP00000339340.3	Q4G0X4
KCTD21	ENST00000908679.1		c.-29-3115G>A	intron	N/A	ENSP00000578738.1
KCTD21	ENST00000908680.1		c.-29-3115G>A	intron	N/A	ENSP00000578739.1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19682

AN:

152086

Hom.:

1361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.0976

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.0206

Gnomad SAS

AF:

0.0863

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.125

AC:

AN:

112

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.143

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.122

AC:

AN:

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.129

AC:

19696

AN:

152204

Hom.:

1362

Cov.:

AF XY:

0.124

AC XY:

9256

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.104

AC:

4338

AN:

41516

American (AMR)

AF:

0.0975

AC:

1491

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

415

AN:

3470

East Asian (EAS)

AF:

0.0207

AC:

107

AN:

5178

South Asian (SAS)

AF:

0.0866

AC:

418

AN:

4826

European-Finnish (FIN)

AF:

0.118

AC:

1256

AN:

10614

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11101

AN:

67986

Other (OTH)

AF:

0.114

AC:

241

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

890

1780

2671

3561

4451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.148

Hom.:

5401

Bravo

AF:

0.128

Asia WGS

AF:

0.0630

AC:

220

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.3

(source)

DANN

Benign

0.70

PhyloP100

0.38

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over