dbSNP rs9536282: KL:c.820-10242C>T (chr13-33043525-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.820-10242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,986 control chromosomes in the GnomAD database, including 3,041 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 0.19 ( 3041 hom., cov: 32)

Consequence

KL
NM_004795.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.415

Publications

5 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=-1.04).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
KL	NM_004795.4 link	c.820-10242C>T	intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3 link	c.-102-10242C>T	intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1 link	c.820-10242C>T	intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1 link	c.820-10242C>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.820-10242C>T		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1 link	n.828-10242C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28416

AN:

151868

Hom.:

3035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.166

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

GnomAD4 genome

AF:

0.187

AC:

28440

AN:

151986

Hom.:

3041

Cov.:

AF XY:

0.186

AC XY:

13841

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.285

AC:

11819

AN:

41434

American (AMR)

AF:

0.121

AC:

1856

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

841

AN:

3466

East Asian (EAS)

AF:

0.00116

AC:

AN:

5166

South Asian (SAS)

AF:

0.172

AC:

828

AN:

4812

European-Finnish (FIN)

AF:

0.193

AC:

2034

AN:

10548

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10569

AN:

67968

Other (OTH)

AF:

0.164

AC:

346

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1157

2314

3470

4627

5784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.168

Hom.:

1217

Bravo

AF:

0.183

Asia WGS

AF:

0.0790

AC:

277

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.7

(source)

DANN

Benign

0.37

PhyloP100

-0.41

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over