rs9527026

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004795.4(KL):c.1155G>A(p.Lys385Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,613,384 control chromosomes in the GnomAD database, including 20,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1939 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18478 hom. )

Consequence

KL
NM_004795.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.370

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 13-33054102-G-A is Benign according to our data. Variant chr13-33054102-G-A is described in ClinVar as [Benign]. Clinvar id is 311692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4 link	c.1155G>A	p.Lys385Lys	synonymous_variant	Exon 2 of 5	ENST00000380099.4	NP_004786.2	Q9UEF7-1
KL	XM_006719895.3 link	c.234G>A	p.Lys78Lys	synonymous_variant	Exon 2 of 5		XP_006719958.1
KL	XM_047430775.1 link	c.1155G>A	p.Lys385Lys	synonymous_variant	Exon 2 of 4		XP_047286731.1
KL	XM_047430776.1 link	c.1155G>A	p.Lys385Lys	synonymous_variant	Exon 2 of 4		XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4 link	c.1155G>A	p.Lys385Lys	synonymous_variant	Exon 2 of 5	1	NM_004795.4	ENSP00000369442.3		Q9UEF7-1
KL	ENST00000487852.1 link	n.1163G>A		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23661

AN:

151758

Hom.:

1938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.141

AC:

35481

AN:

251310

Hom.:

2963

AF XY:

0.146

AC XY:

19872

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.0734

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.154

AC:

225453

AN:

1461508

Hom.:

18478

Cov.:

AF XY:

0.155

AC XY:

112659

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.0770

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.000856

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.156

AC:

23674

AN:

151876

Hom.:

1939

Cov.:

AF XY:

0.157

AC XY:

11651

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.000967

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.158

Hom.:

1108

Bravo

AF:

0.148

Asia WGS

AF:

0.0750

AC:

264

AN:

3478

EpiCase

AF:

0.154

EpiControl

AF:

0.155

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Tumoral calcinosis, hyperphosphatemic, familial, 3

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.1

DANN

Benign

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over