rs9536254

Positions:

• chr13-33038142-T-G

Variant summary

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

The NM_004795.4(KL):​c.820-15625T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 152,298 control chromosomes in the GnomAD database, including 319 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 0.062 (319 hom., cov: 33)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

Genes affected

KL (HGNC:6344): (klotho) This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]

KL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.820-15625T>G		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-15625T>G		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.820-15625T>G		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.820-15625T>G		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.820-15625T>G		intron_variant		1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-15625T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9490 AN: 152180 Hom.: 318 Cov.: 33

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0575

Gnomad FIN AF: 0.0810

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0670

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

GnomAD4 genome AF: 0.0624 AC: 9498 AN: 152298 Hom.: 319 Cov.: 33 AF XY: 0.0623 AC XY: 4637 AN XY: 74466

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.0520

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.0810

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.0663

Alfa AF: 0.0696 Hom.: 48

Bravo AF: 0.0590

Asia WGS AF: 0.0320 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.84

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: rs9536254; hg19: chr13-33612279;