Genetic Variant KLHL20:c.852-120A>G (chr1-173755803-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014458.4(KLHL20):c.852-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 611,504 control chromosomes in the GnomAD database, including 21,687 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 0.23 ( 4436 hom., cov: 32)

Exomes 𝑓: 0.27 ( 17251 hom. )

Consequence

KLHL20
NM_014458.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0510

Publications

12 publications found

Variant links:

Genes affected

KLHL20 (HGNC:25056): (kelch like family member 20) The protein encoded by this gene is a member of the kelch family of proteins, which is characterized by a 44-56 amino acid repeat motif. The kelch motif appears in many different polypeptide contexts and contains multiple potential protein-protein contact sites. Members of this family are present both throughout the cell and extracellularly, with diverse activities. [provided by RefSeq, Jul 2008]

KLHL20 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

KLHL20 links:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014458.4. 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
	KLHL20	NM_014458.4	MANE Select	c.852-120A>G		intron	N/A	NP_055273.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL20	ENST00000209884.5	TSL:1 MANE Select	c.852-120A>G		intron	N/A	ENSP00000209884.4

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34769

AN:

151990

Hom.:

4440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.240

GnomAD4 exome

AF:

0.269

AC:

123387

AN:

459394

Hom.:

17251

AF XY:

0.269

AC XY:

65291

AN XY:

242940

show subpopulations

African (AFR)

AF:

0.110

AC:

1290

AN:

11778

American (AMR)

AF:

0.204

AC:

3564

AN:

17488

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

5391

AN:

13698

East Asian (EAS)

AF:

0.272

AC:

8058

AN:

29618

South Asian (SAS)

AF:

0.247

AC:

10812

AN:

43732

European-Finnish (FIN)

AF:

0.232

AC:

8486

AN:

36630

Middle Eastern (MID)

AF:

0.337

AC:

1180

AN:

3506

European-Non Finnish (NFE)

AF:

0.280

AC:

77653

AN:

277258

Other (OTH)

AF:

0.271

AC:

6953

AN:

25686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4117

8234

12352

16469

20586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.229

AC:

34773

AN:

152110

Hom.:

4436

Cov.:

AF XY:

0.227

AC XY:

16869

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.112

AC:

4647

AN:

41530

American (AMR)

AF:

0.233

AC:

3558

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

1407

AN:

3466

East Asian (EAS)

AF:

0.292

AC:

1507

AN:

5164

South Asian (SAS)

AF:

0.245

AC:

1180

AN:

4820

European-Finnish (FIN)

AF:

0.225

AC:

2379

AN:

10570

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.283

AC:

19219

AN:

67962

Other (OTH)

AF:

0.238

AC:

503

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1330

2660

3989

5319

6649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.270

Hom.:

3784

Bravo

AF:

0.225

Asia WGS

AF:

0.241

AC:

840

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.2

(source)

DANN

Benign

0.70

PhyloP100

-0.051

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