Variant rs650439 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004795.4(KL):c.2701+22T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 1,609,134 control chromosomes in the GnomAD database, including 570,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 50275 hom., cov: 31)

Exomes 𝑓: 0.84 ( 520598 hom. )

Consequence

KL
NM_004795.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.97

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 13-33061802-T-A is Benign according to our data. Variant chr13-33061802-T-A is described in ClinVar as [Benign]. Clinvar id is 1222763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4 linkuse as main transcript	c.2701+22T>A		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3 linkuse as main transcript	c.1780+22T>A		intron_variant			XP_006719958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4 linkuse as main transcript	c.2701+22T>A		intron_variant		1	NM_004795.4	ENSP00000369442	P1	Q9UEF7-1
KL	ENST00000487852.1 linkuse as main transcript	n.2759+22T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.809

AC:

123066

AN:

152040

Hom.:

50237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.874

Gnomad AMR

AF:

0.812

Gnomad ASJ

AF:

0.913

Gnomad EAS

AF:

0.615

Gnomad SAS

AF:

0.803

Gnomad FIN

AF:

0.885

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.856

Gnomad OTH

AF:

0.838

GnomAD3 exomes

AF:

0.819

AC:

200289

AN:

244550

Hom.:

82822

AF XY:

0.823

AC XY:

109260

AN XY:

132686

show subpopulations

Gnomad AFR exome

AF:

0.725

Gnomad AMR exome

AF:

0.796

Gnomad ASJ exome

AF:

0.907

Gnomad EAS exome

AF:

0.602

Gnomad SAS exome

AF:

0.814

Gnomad FIN exome

AF:

0.882

Gnomad NFE exome

AF:

0.857

Gnomad OTH exome

AF:

0.842

GnomAD4 exome

AF:

0.844

AC:

1229547

AN:

1456976

Hom.:

520598

Cov.:

AF XY:

0.844

AC XY:

611919

AN XY:

724878

show subpopulations

Gnomad4 AFR exome

AF:

0.725

Gnomad4 AMR exome

AF:

0.803

Gnomad4 ASJ exome

AF:

0.910

Gnomad4 EAS exome

AF:

0.627

Gnomad4 SAS exome

AF:

0.815

Gnomad4 FIN exome

AF:

0.882

Gnomad4 NFE exome

AF:

0.856

Gnomad4 OTH exome

AF:

0.834

GnomAD4 genome

AF:

0.809

AC:

123154

AN:

152158

Hom.:

50275

Cov.:

AF XY:

0.809

AC XY:

60155

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.726

Gnomad4 AMR

AF:

0.812

Gnomad4 ASJ

AF:

0.913

Gnomad4 EAS

AF:

0.615

Gnomad4 SAS

AF:

0.803

Gnomad4 FIN

AF:

0.885

Gnomad4 NFE

AF:

0.856

Gnomad4 OTH

AF:

0.837

Alfa

AF:

0.840

Hom.:

9922

Bravo

AF:

0.803

Asia WGS

AF:

0.712

AC:

2479

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Tumoral calcinosis, hyperphosphatemic, familial, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0020

DANN

Benign

0.51

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