Genetic Variant NM_014851.4:c.*1697G>A (chr1-6591668-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_014851.4(KLHL21):c.*1697G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,194 control chromosomes in the GnomAD database, including 6,088 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 0.28 ( 6079 hom., cov: 33)

Exomes 𝑓: 0.36 ( 9 hom. )

Consequence

KLHL21
NM_014851.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

25 publications found

Variant links:

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]

KLHL21 links:

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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=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL21	NM_014851.4	MANE Select	c.*1697G>A		3_prime_UTR	Exon 4 of 4	NP_055666.2
	KLHL21	NM_001324309.2		c.*2440G>A		3_prime_UTR	Exon 4 of 4	NP_001311238.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL21	ENST00000377658.8	TSL:1 MANE Select	c.*1697G>A		3_prime_UTR	Exon 4 of 4	ENSP00000366886.4
	KLHL21	ENST00000377663.3	TSL:1	c.*3697G>A		3_prime_UTR	Exon 3 of 3	ENSP00000366891.3

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42247

AN:

151948

Hom.:

6076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.298

GnomAD4 exome

AF:

0.359

AC:

AN:

128

Hom.:

Cov.:

AF XY:

0.391

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.400

AC:

AN:

110

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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:

0.278

AC:

42255

AN:

152066

Hom.:

6079

Cov.:

AF XY:

0.276

AC XY:

20518

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.220

AC:

9145

AN:

41506

American (AMR)

AF:

0.249

AC:

3809

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1178

AN:

3468

East Asian (EAS)

AF:

0.145

AC:

748

AN:

5166

South Asian (SAS)

AF:

0.295

AC:

1421

AN:

4816

European-Finnish (FIN)

AF:

0.272

AC:

2888

AN:

10602

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22082

AN:

67898

Other (OTH)

AF:

0.298

AC:

629

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1581

3163

4744

6326

7907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.316

Hom.:

12283

Bravo

AF:

0.271

Asia WGS

AF:

0.202

AC:

706

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.64

(source)

DANN

Benign

0.67

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over