rs483731

Positions:

• chr11-78177698-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD21	NM_001029859.3	c.-29-3115G>A		intron_variant		ENST00000340067.4	NP_001025030.1
KCTD21	XM_047426803.1	c.-568G>A		5_prime_UTR_variant	2/3		XP_047282759.1
KCTD21	XM_006718517.3	c.-30+41G>A		intron_variant			XP_006718580.1
KCTD21	XM_006718518.4	c.-29-3115G>A		intron_variant			XP_006718581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD21	ENST00000340067.4	c.-29-3115G>A		intron_variant		1	NM_001029859.3	ENSP00000339340.3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19682 AN: 152086 Hom.: 1361 Cov.: 32

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: 14 AN: 112 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 10 AN XY: 80

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.129 AC: 19696 AN: 152204 Hom.: 1362 Cov.: 32 AF XY: 0.124 AC XY: 9256 AN XY: 74408

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0975

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0207

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.114

Alfa AF: 0.149 Hom.: 2398

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
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs483731; hg19: chr11-77888744;