1-6591033-G-A

Position:

• chr1-6591033-G-A

Variant summary

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

The ENST00000377658.8(KLHL21):​c.*2332C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 398,592 control chromosomes in the GnomAD database, including 5,676 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 0.12 (1476 hom., cov: 33)
  • Exomes 𝑓: 0.16 (4200 hom.)
• Consequence: KLHL21 ENST00000377658.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

KLHL21 (HGNC:29041): (kelch like family member 21) Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in polar microtubule. Part of Cul3-RING ubiquitin ligase complex. [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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL21	NM_014851.4	c.*2332C>T		3_prime_UTR_variant	4/4	ENST00000377658.8	NP_055666.2
KLHL21	NM_001324309.2	c.*3075C>T		3_prime_UTR_variant	4/4		NP_001311238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL21	ENST00000377658.8	c.*2332C>T		3_prime_UTR_variant	4/4	1	NM_014851.4	ENSP00000366886	P1
KLHL21	ENST00000377663.3	c.*4332C>T		3_prime_UTR_variant	3/3	1		ENSP00000366891

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17700 AN: 152164 Hom.: 1478 Cov.: 33

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0962

GnomAD4 exome AF: 0.160 AC: 39453 AN: 246310 Hom.: 4200 Cov.: 0 AF XY: 0.159 AC XY: 19830 AN XY: 124814

Gnomad4 AFR exome AF: 0.0284

Gnomad4 AMR exome AF: 0.0645

Gnomad4 ASJ exome AF: 0.0491

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.116 AC: 17695 AN: 152282 Hom.: 1476 Cov.: 33 AF XY: 0.117 AC XY: 8683 AN XY: 74452

Gnomad4 AFR AF: 0.0291

Gnomad4 AMR AF: 0.0810

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.132 Hom.: 2001

Bravo AF: 0.107

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.66
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1

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: rs201171; hg19: chr1-6651093;