rs7674434

Positions:

• chr4-39417789-T-G

Variant summary

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

The NM_175737.4(KLB):​c.825+10015T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,030 control chromosomes in the GnomAD database, including 8,317 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 0.32 (8317 hom., cov: 31)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLB	NM_175737.4	c.825+10015T>G		intron_variant		ENST00000257408.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLB	ENST00000257408.5	c.825+10015T>G		intron_variant		1	NM_175737.4	P1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48024 AN: 151912 Hom.: 8314 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.316 AC: 48040 AN: 152030 Hom.: 8317 Cov.: 31 AF XY: 0.314 AC XY: 23327 AN XY: 74302

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.289

Alfa AF: 0.277 Hom.: 12190

Bravo AF: 0.316

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.86

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: rs7674434; hg19: chr4-39419409;