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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KCTD21	NM_001029859.3 link	c.-29-3115G>A	intron_variant	Intron 1 of 1	ENST00000340067.4	NP_001025030.1	Q4G0X4
KCTD21	XM_047426803.1 link	c.-568G>A	5_prime_UTR_variant	Exon 2 of 3		XP_047282759.1
KCTD21	XM_006718517.3 link	c.-30+41G>A	intron_variant	Intron 2 of 2		XP_006718580.1	Q4G0X4
KCTD21	XM_006718518.4 link	c.-29-3115G>A	intron_variant	Intron 1 of 1		XP_006718581.1	Q4G0X4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD21	ENST00000340067.4 link	c.-29-3115G>A		intron_variant	Intron 1 of 1	1	NM_001029859.3	ENSP00000339340.3		Q4G0X4

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over