Genetic Variant KL:c.820-5022C>T (chr13-33048745-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_004795.4(KL):c.820-5022C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,062 control chromosomes in the GnomAD database, including 34,142 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 0.67 ( 34142 hom., cov: 32)

Consequence

KL
NM_004795.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.19

Publications

2 publications found

Variant links:

Genes affected

KL (HGNC:6344): (klotho) This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]

KL Gene-Disease associations (from GenCC):

tumoral calcinosis, hyperphosphatemic, familial, 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
tumoral calcinosis, hyperphosphatemic, familial, 3
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

KL 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=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
KL	NM_004795.4 link	c.820-5022C>T	intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3 link	c.-102-5022C>T	intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1 link	c.820-5022C>T	intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1 link	c.820-5022C>T	intron_variant	Intron 1 of 3		XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4 link	c.820-5022C>T		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1 link	n.828-5022C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

101079

AN:

151944

Hom.:

34102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.552

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.704

Gnomad SAS

AF:

0.660

Gnomad FIN

AF:

0.704

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.694

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.665

AC:

101170

AN:

152062

Hom.:

34142

Cov.:

AF XY:

0.667

AC XY:

49565

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.552

AC:

22890

AN:

41468

American (AMR)

AF:

0.763

AC:

11664

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.692

AC:

2403

AN:

3472

East Asian (EAS)

AF:

0.705

AC:

3643

AN:

5170

South Asian (SAS)

AF:

0.659

AC:

3161

AN:

4800

European-Finnish (FIN)

AF:

0.704

AC:

7435

AN:

10554

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.700

AC:

47588

AN:

67994

Other (OTH)

AF:

0.695

AC:

1469

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1710

3420

5130

6840

8550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.695

Hom.:

139533

Bravo

AF:

0.670

Asia WGS

AF:

0.691

AC:

2404

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.61

(source)

DANN

Benign

0.35

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over