rs11940694

Positions:

• chr4-39413373-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_175737.4(KLB):​c.825+5599A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,958 control chromosomes in the GnomAD database, including 24,948 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 0.57 (24948 hom., cov: 31)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLB	NM_175737.4	c.825+5599A>G		intron_variant		ENST00000257408.5	NP_783864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLB	ENST00000257408.5	c.825+5599A>G		intron_variant		1	NM_175737.4	ENSP00000257408.4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86230 AN: 151840 Hom.: 24915 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.568 AC: 86299 AN: 151958 Hom.: 24948 Cov.: 31 AF XY: 0.564 AC XY: 41903 AN XY: 74280

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.549

Alfa AF: 0.576 Hom.: 42842

Bravo AF: 0.555

Asia WGS AF: 0.504 AC: 1752 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	23
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.60		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.60		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11940694; hg19: chr4-39414993;