dbSNP rs2273366: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL20	NM_014458.4 link	c.852-120A>G		intron_variant	Intron 5 of 11	ENST00000209884.5	NP_055273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL20	ENST00000209884.5 link	c.852-120A>G		intron_variant	Intron 5 of 11	1	NM_014458.4	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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over