chr4-39426675-C-T

Position:

• chr4-39426675-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175737.4(KLB):​c.826-7535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 136,378 control chromosomes in the GnomAD database, including 2,343 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 0.18 (2343 hom., cov: 31)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLB	NM_175737.4	c.826-7535C>T		intron_variant		ENST00000257408.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLB	ENST00000257408.5	c.826-7535C>T		intron_variant		1	NM_175737.4	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 24440 AN: 136270 Hom.: 2342 Cov.: 31

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.179 AC: 24444 AN: 136378 Hom.: 2343 Cov.: 31 AF XY: 0.182 AC XY: 11858 AN XY: 65318

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.179

Alfa AF: 0.196 Hom.: 3007

Bravo AF: 0.152

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.7
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs17431867; hg19: chr4-39428295;