dbSNP rs495392: KL:c.819+796C>A (chr13-33018055-C-A) – 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.819+796C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,104 control chromosomes in the GnomAD database, including 4,887 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 0.24 ( 4887 hom., cov: 33)

Consequence

KL
NM_004795.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.544

Publications

19 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:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4 link	c.819+796C>A	intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2	Q9UEF7-1
KL	XM_006719895.3 link	c.-103+1742C>A	intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1 link	c.819+796C>A	intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1 link	c.819+796C>A	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.819+796C>A		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3		Q9UEF7-1
KL	ENST00000487852.1 link	n.827+796C>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36553

AN:

151986

Hom.:

4877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.248

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

GnomAD4 genome

AF:

0.240

AC:

36577

AN:

152104

Hom.:

4887

Cov.:

AF XY:

0.241

AC XY:

17948

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.123

AC:

5086

AN:

41496

American (AMR)

AF:

0.330

AC:

5048

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

879

AN:

3470

East Asian (EAS)

AF:

0.192

AC:

992

AN:

5172

South Asian (SAS)

AF:

0.252

AC:

1214

AN:

4824

European-Finnish (FIN)

AF:

0.312

AC:

3300

AN:

10562

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.283

AC:

19252

AN:

67980

Other (OTH)

AF:

0.251

AC:

529

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1408

2817

4225

5634

7042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.271

Hom.:

10626

Bravo

AF:

0.239

Asia WGS

AF:

0.260

AC:

904

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.75

(source)

DANN

Benign

0.33

PhyloP100

-0.54

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