1-6591033-G-A

Variant names:

• chr1-6591033-G-A
• rs201171
• NM_014851.4:c.*2332C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014851.4(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 NM_014851.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014851.4. 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
	KLHL21	NM_014851.4	MANE Select	c.*2332C>T		3_prime_UTR	Exon 4 of 4	NP_055666.2
	KLHL21	NM_001324309.2		c.*3075C>T		3_prime_UTR	Exon 4 of 4	NP_001311238.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL21	ENST00000377658.8	TSL:1 MANE Select	c.*2332C>T		3_prime_UTR	Exon 4 of 4	ENSP00000366886.4	Q9UJP4-1
	KLHL21	ENST00000377663.3	TSL:1	c.*4332C>T		3_prime_UTR	Exon 3 of 3	ENSP00000366891.3	Q9UJP4-2

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

African (AFR) AF: 0.0284 AC: 204 AN: 7180

American (AMR) AF: 0.0645 AC: 479 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.0491 AC: 454 AN: 9240

East Asian (EAS) AF: 0.397 AC: 9094 AN: 22894

South Asian (SAS) AF: 0.118 AC: 359 AN: 3032

European-Finnish (FIN) AF: 0.168 AC: 3494 AN: 20832

Middle Eastern (MID) AF: 0.0440 AC: 57 AN: 1294

European-Non Finnish (NFE) AF: 0.146 AC: 23073 AN: 158032

Other (OTH) AF: 0.137 AC: 2239 AN: 16374

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

African (AFR) AF: 0.0291 AC: 1209 AN: 41586

American (AMR) AF: 0.0810 AC: 1239 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3472

East Asian (EAS) AF: 0.400 AC: 2072 AN: 5174

South Asian (SAS) AF: 0.107 AC: 518 AN: 4828

European-Finnish (FIN) AF: 0.168 AC: 1776 AN: 10600

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10323 AN: 68000

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.131 Hom.: 2816

Bravo AF: 0.107

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.66
PhyloP100		0.055
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs201171; hg19: chr1-6651093;