4-39429811-T-C

Variant names:

• chr4-39429811-T-C
• rs2608819
• NM_175737.4:c.826-4399T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175737.4(KLB):​c.826-4399T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,130 control chromosomes in the GnomAD database, including 47,272 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 0.77 (47272 hom., cov: 32)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175737.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLB	NM_175737.4	MANE Select	c.826-4399T>C		intron	N/A	NP_783864.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLB	ENST00000257408.5	TSL:1 MANE Select	c.826-4399T>C		intron	N/A	ENSP00000257408.4
	KLB	ENST00000859482.1		c.826-4399T>C		intron	N/A	ENSP00000529541.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116495 AN: 152012 Hom.: 47261 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.766 AC: 116540 AN: 152130 Hom.: 47272 Cov.: 32 AF XY: 0.769 AC XY: 57200 AN XY: 74360

African (AFR) AF: 0.471 AC: 19531 AN: 41464

American (AMR) AF: 0.835 AC: 12748 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2808 AN: 3470

East Asian (EAS) AF: 0.835 AC: 4317 AN: 5172

South Asian (SAS) AF: 0.802 AC: 3872 AN: 4830

European-Finnish (FIN) AF: 0.925 AC: 9795 AN: 10590

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60736 AN: 68018

Other (OTH) AF: 0.785 AC: 1651 AN: 2104

Alfa AF: 0.848 Hom.: 88361

Bravo AF: 0.748

Asia WGS AF: 0.790 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.55
DANN	Benign	0.47
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2608819; hg19: chr4-39431431;