rs17431867

Variant names:

• chr4-39426675-C-T
• rs17431867
• NM_175737.4:c.826-7535C>T

Variant summary

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

The NM_175737.4(KLB):​c.826-7535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 136,378 control chromosomes in the GnomAD database, including 2,343 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 0.18 (2343 hom., cov: 31)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLB	NM_175737.4	MANE Select	c.826-7535C>T		intron	N/A	NP_783864.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLB	ENST00000257408.5	TSL:1 MANE Select	c.826-7535C>T		intron	N/A	ENSP00000257408.4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 24440 AN: 136270 Hom.: 2342 Cov.: 31

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.179 AC: 24444 AN: 136378 Hom.: 2343 Cov.: 31 AF XY: 0.182 AC XY: 11858 AN XY: 65318

African (AFR) AF: 0.0917 AC: 3550 AN: 38732

American (AMR) AF: 0.156 AC: 1822 AN: 11648

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 671 AN: 3270

East Asian (EAS) AF: 0.138 AC: 636 AN: 4620

South Asian (SAS) AF: 0.154 AC: 604 AN: 3924

European-Finnish (FIN) AF: 0.265 AC: 2152 AN: 8108

Middle Eastern (MID) AF: 0.208 AC: 54 AN: 260

European-Non Finnish (NFE) AF: 0.230 AC: 14546 AN: 63214

Other (OTH) AF: 0.179 AC: 323 AN: 1804

Alfa AF: 0.190 Hom.: 3909

Bravo AF: 0.152

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.7
DANN	Benign	0.71
PhyloP100		0.045
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: rs17431867; hg19: chr4-39428295;