rs9536282

Variant names:

• chr13-33043525-C-T
• rs9536282
• NM_004795.4:c.820-10242C>T

Variant summary

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

The NM_004795.4(KL):​c.820-10242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,986 control chromosomes in the GnomAD database, including 3,041 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 0.19 (3041 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.820-10242C>T		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-10242C>T		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.820-10242C>T		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.820-10242C>T		intron_variant	Intron 1 of 3		XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.820-10242C>T		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-10242C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28416 AN: 151868 Hom.: 3035 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.187 AC: 28440 AN: 151986 Hom.: 3041 Cov.: 32 AF XY: 0.186 AC XY: 13841 AN XY: 74284

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.164

Alfa AF: 0.167 Hom.: 1058

Bravo AF: 0.183

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.37

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: rs9536282; hg19: chr13-33617662;