chr4-39408562-T-A

Variant summary

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

The NM_175737.4(KLB):​c.825+788T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,144 control chromosomes in the GnomAD database, including 3,123 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 0.20 ( 3123 hom., cov: 32)

Consequence

KLB
NM_175737.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.256
Variant links:
Genes affected
KLB (HGNC:15527): (klotho beta) Enables fibroblast growth factor binding activity and fibroblast growth factor receptor binding activity. Predicted to be involved in fibroblast growth factor receptor signaling pathway. Predicted to act upstream of or within positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway and positive regulation of cell population proliferation. Predicted to be located in plasma membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLBNM_175737.4 linkuse as main transcriptc.825+788T>A intron_variant ENST00000257408.5 NP_783864.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLBENST00000257408.5 linkuse as main transcriptc.825+788T>A intron_variant 1 NM_175737.4 ENSP00000257408 P1

Frequencies

GnomAD3 genomes
AF:
0.198
AC:
30115
AN:
152026
Hom.:
3121
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.191
Gnomad AMI
AF:
0.185
Gnomad AMR
AF:
0.206
Gnomad ASJ
AF:
0.158
Gnomad EAS
AF:
0.384
Gnomad SAS
AF:
0.187
Gnomad FIN
AF:
0.227
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.185
Gnomad OTH
AF:
0.201
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.198
AC:
30133
AN:
152144
Hom.:
3123
Cov.:
32
AF XY:
0.200
AC XY:
14894
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.191
Gnomad4 AMR
AF:
0.205
Gnomad4 ASJ
AF:
0.158
Gnomad4 EAS
AF:
0.384
Gnomad4 SAS
AF:
0.186
Gnomad4 FIN
AF:
0.227
Gnomad4 NFE
AF:
0.185
Gnomad4 OTH
AF:
0.205
Alfa
AF:
0.198
Hom.:
386
Bravo
AF:
0.198
Asia WGS
AF:
0.332
AC:
1143
AN:
3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
6.1
DANN
Benign
0.69

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: rs12647895; hg19: chr4-39410182; API