Genetic Variant KL:c.820-3729T>C (chr13-33050038-T-C) – 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.820-3729T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,114 control chromosomes in the GnomAD database, including 8,976 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 0.31 ( 8976 hom., cov: 33)

Consequence

KL
NM_004795.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.106

Publications

4 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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
KL	NM_004795.4 link	c.820-3729T>C	intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3 link	c.-102-3729T>C	intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1 link	c.820-3729T>C	intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1 link	c.820-3729T>C	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.820-3729T>C		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1 link	n.828-3729T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46919

AN:

151996

Hom.:

8964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0897

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.338

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

GnomAD4 genome

AF:

0.309

AC:

46940

AN:

152114

Hom.:

8976

Cov.:

AF XY:

0.308

AC XY:

22908

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0896

AC:

3721

AN:

41548

American (AMR)

AF:

0.450

AC:

6871

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1451

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

877

AN:

5180

South Asian (SAS)

AF:

0.305

AC:

1468

AN:

4814

European-Finnish (FIN)

AF:

0.381

AC:

4012

AN:

10544

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.402

AC:

27318

AN:

67976

Other (OTH)

AF:

0.343

AC:

722

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1493

2986

4478

5971

7464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.377

Hom.:

11113

Bravo

AF:

0.308

Asia WGS

AF:

0.270

AC:

942

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.1

(source)

DANN

Benign

0.74

PhyloP100

-0.11

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

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