chr4-39429349-C-T

Position:

• chr4-39429349-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.826-4861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,004 control chromosomes in the GnomAD database, including 29,861 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 0.61 (29861 hom., cov: 32)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.686

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLB	NM_175737.4	c.826-4861C>T		intron_variant		ENST00000257408.5	NP_783864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLB	ENST00000257408.5	c.826-4861C>T		intron_variant		1	NM_175737.4	ENSP00000257408.4

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93205 AN: 151884 Hom.: 29843 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.613 AC: 93247 AN: 152004 Hom.: 29861 Cov.: 32 AF XY: 0.617 AC XY: 45834 AN XY: 74280

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.636

Alfa AF: 0.661 Hom.: 57604

Bravo AF: 0.605

Asia WGS AF: 0.669 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1979283; hg19: chr4-39430969;