dbSNP rs9526984: KL:c.820-17967A>G (chr13-33035800-A-G) – 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.820-17967A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 152,262 control chromosomes in the GnomAD database, including 299 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 0.055 ( 299 hom., cov: 32)

Consequence

KL
NM_004795.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0970

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=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4 link	c.820-17967A>G	intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2	Q9UEF7-1
KL	XM_006719895.3 link	c.-102-17967A>G	intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1 link	c.820-17967A>G	intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1 link	c.820-17967A>G	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.820-17967A>G		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3		Q9UEF7-1
KL	ENST00000487852.1 link	n.828-17967A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0553

AC:

8410

AN:

152144

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0501

Gnomad ASJ

AF:

0.0865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0571

Gnomad FIN

AF:

0.0810

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0802

Gnomad OTH

AF:

0.0599

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

GnomAD4 genome

AF:

0.0552

AC:

8412

AN:

152262

Hom.:

299

Cov.:

AF XY:

0.0553

AC XY:

4115

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0138

AC:

572

AN:

41562

American (AMR)

AF:

0.0499

AC:

763

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0865

AC:

300

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.0576

AC:

278

AN:

4826

European-Finnish (FIN)

AF:

0.0810

AC:

859

AN:

10610

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0802

AC:

5453

AN:

67994

Other (OTH)

AF:

0.0593

AC:

125

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

399

798

1196

1595

1994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0729

Hom.:

612

Bravo

AF:

0.0510

Asia WGS

AF:

0.0290

AC:

104

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.2

(source)

DANN

Benign

0.28

PhyloP100

-0.097

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