13-33025521-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004795.4(KL):​c.819+8262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,006 control chromosomes in the GnomAD database, including 28,293 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 0.59 ( 28293 hom., cov: 32)

Consequence

KL
NM_004795.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.615
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KLNM_004795.4 linkc.819+8262A>G intron_variant Intron 1 of 4 ENST00000380099.4 NP_004786.2 Q9UEF7-1
KLXM_006719895.3 linkc.-103+9208A>G intron_variant Intron 1 of 4 XP_006719958.1
KLXM_047430775.1 linkc.819+8262A>G intron_variant Intron 1 of 3 XP_047286731.1
KLXM_047430776.1 linkc.819+8262A>G intron_variant Intron 1 of 3 XP_047286732.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLENST00000380099.4 linkc.819+8262A>G intron_variant Intron 1 of 4 1 NM_004795.4 ENSP00000369442.3 Q9UEF7-1
KLENST00000487852.1 linkn.827+8262A>G intron_variant Intron 1 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.590
AC:
89562
AN:
151888
Hom.:
28284
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.338
Gnomad AMI
AF:
0.805
Gnomad AMR
AF:
0.663
Gnomad ASJ
AF:
0.660
Gnomad EAS
AF:
0.635
Gnomad SAS
AF:
0.634
Gnomad FIN
AF:
0.701
Gnomad MID
AF:
0.725
Gnomad NFE
AF:
0.694
Gnomad OTH
AF:
0.635
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.589
AC:
89598
AN:
152006
Hom.:
28293
Cov.:
32
AF XY:
0.592
AC XY:
43967
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.338
Gnomad4 AMR
AF:
0.663
Gnomad4 ASJ
AF:
0.660
Gnomad4 EAS
AF:
0.634
Gnomad4 SAS
AF:
0.633
Gnomad4 FIN
AF:
0.701
Gnomad4 NFE
AF:
0.694
Gnomad4 OTH
AF:
0.635
Alfa
AF:
0.591
Hom.:
4036
Bravo
AF:
0.580
Asia WGS
AF:
0.636
AC:
2213
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
5.8
DANN
Benign
0.77

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.

Other links and lift over

dbSNP: rs565587; hg19: chr13-33599659; API