dbSNP rs685417: KL:c.820-14772G>A (chr13-33038995-G-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.820-14772G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,914 control chromosomes in the GnomAD database, including 29,119 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 0.60 ( 29119 hom., cov: 32)

Consequence

KL
NM_004795.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.676

Publications

15 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4 link	c.820-14772G>A	intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2	Q9UEF7-1
KL	XM_006719895.3 link	c.-102-14772G>A	intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1 link	c.820-14772G>A	intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1 link	c.820-14772G>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.820-14772G>A		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3		Q9UEF7-1
KL	ENST00000487852.1 link	n.828-14772G>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91478

AN:

151796

Hom.:

29108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.805

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.682

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.703

Gnomad MID

AF:

0.726

Gnomad NFE

AF:

0.695

Gnomad OTH

AF:

0.645

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

GnomAD4 genome

AF:

0.602

AC:

91519

AN:

151914

Hom.:

29119

Cov.:

AF XY:

0.605

AC XY:

44921

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.374

AC:

15489

AN:

41392

American (AMR)

AF:

0.668

AC:

10206

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.660

AC:

2288

AN:

3466

East Asian (EAS)

AF:

0.682

AC:

3519

AN:

5160

South Asian (SAS)

AF:

0.637

AC:

3068

AN:

4814

European-Finnish (FIN)

AF:

0.703

AC:

7417

AN:

10554

Middle Eastern (MID)

AF:

0.723

AC:

211

AN:

292

European-Non Finnish (NFE)

AF:

0.695

AC:

47220

AN:

67940

Other (OTH)

AF:

0.647

AC:

1367

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1703

3407

5110

6814

8517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.670

Hom.:

50226

Bravo

AF:

0.594

Asia WGS

AF:

0.654

AC:

2269

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.58

(source)

DANN

Benign

0.80

PhyloP100

-0.68

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