chr11-78179683-A-G

Position:

• chr11-78179683-A-G

Variant summary

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

The NM_001029859.3(KCTD21):​c.-29-5100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,696 control chromosomes in the GnomAD database, including 23,921 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 0.56 (23921 hom., cov: 31)
• Consequence: KCTD21 NM_001029859.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD21	NM_001029859.3	c.-29-5100T>C		intron_variant		ENST00000340067.4	NP_001025030.1
KCTD21	XM_006718517.3	c.-276-1698T>C		intron_variant			XP_006718580.1
KCTD21	XM_006718518.4	c.-29-5100T>C		intron_variant			XP_006718581.1
KCTD21	XM_047426803.1	c.-855-1698T>C		intron_variant			XP_047282759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD21	ENST00000340067.4	c.-29-5100T>C		intron_variant		1	NM_001029859.3	ENSP00000339340	P1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84552 AN: 151578 Hom.: 23907 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.558 AC: 84607 AN: 151696 Hom.: 23921 Cov.: 31 AF XY: 0.558 AC XY: 41335 AN XY: 74132

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.565

Alfa AF: 0.563 Hom.: 11756

Bravo AF: 0.564

Asia WGS AF: 0.575 AC: 2001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.30
DANN	Benign	0.36

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: rs230656; hg19: chr11-77890729;