13-33026095-T-C

Position:

• chr13-33026095-T-C

Variant summary

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

The NM_004795.4(KL):​c.819+8836T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,102 control chromosomes in the GnomAD database, including 14,052 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 0.42 (14052 hom., cov: 31)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.819+8836T>C		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-103+9782T>C		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.819+8836T>C		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.819+8836T>C		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.819+8836T>C		intron_variant		1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.827+8836T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63916 AN: 151984 Hom.: 14049 Cov.: 31

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.420 AC: 63934 AN: 152102 Hom.: 14052 Cov.: 31 AF XY: 0.425 AC XY: 31579 AN XY: 74356

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.432

Alfa AF: 0.434 Hom.: 8220

Bravo AF: 0.401

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.60

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: rs571118; hg19: chr13-33600233;