rs1982738

Positions:

• chr4-39410641-C-T

Variant summary

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

The ENST00000257408.5(KLB):​c.825+2867C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,044 control chromosomes in the GnomAD database, including 4,509 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 0.24 (4509 hom., cov: 31)
• Consequence: KLB ENST00000257408.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLB	NM_175737.4	c.825+2867C>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.825+2867C>T		intron_variant		1	NM_175737.4	ENSP00000257408	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35825 AN: 151926 Hom.: 4489 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.236 AC: 35881 AN: 152044 Hom.: 4509 Cov.: 31 AF XY: 0.236 AC XY: 17520 AN XY: 74308

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.222

Alfa AF: 0.224 Hom.: 498

Bravo AF: 0.235

Asia WGS AF: 0.340 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.82

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: rs1982738; hg19: chr4-39412261;