13-33043037-T-G

Position:

• chr13-33043037-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.820-10730T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,016 control chromosomes in the GnomAD database, including 9,905 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 0.35 (9905 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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 (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.820-10730T>G		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-10730T>G		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.820-10730T>G		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.820-10730T>G		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.820-10730T>G		intron_variant		1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-10730T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53512 AN: 151898 Hom.: 9903 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.352 AC: 53535 AN: 152016 Hom.: 9905 Cov.: 32 AF XY: 0.355 AC XY: 26390 AN XY: 74292

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.368

Alfa AF: 0.373 Hom.: 11934

Bravo AF: 0.340

Asia WGS AF: 0.417 AC: 1451 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	2.5
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2320762; hg19: chr13-33617174;