13-33051007-C-T

Variant names:

• chr13-33051007-C-T
• rs560014
• NM_004795.4:c.820-2760C>T

Variant summary

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

The NM_004795.4(KL):​c.820-2760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,094 control chromosomes in the GnomAD database, including 8,960 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 0.31 (8960 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• tumoral calcinosis, hyperphosphatemic, familial, 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• tumoral calcinosis, hyperphosphatemic, familial, 3

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.820-2760C>T		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-2760C>T		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.820-2760C>T		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.820-2760C>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.820-2760C>T		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-2760C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46863 AN: 151976 Hom.: 8949 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.308 AC: 46883 AN: 152094 Hom.: 8960 Cov.: 32 AF XY: 0.308 AC XY: 22877 AN XY: 74322

African (AFR) AF: 0.0894 AC: 3715 AN: 41536

American (AMR) AF: 0.450 AC: 6878 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3468

East Asian (EAS) AF: 0.169 AC: 873 AN: 5156

South Asian (SAS) AF: 0.304 AC: 1466 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4031 AN: 10550

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27243 AN: 67968

Other (OTH) AF: 0.343 AC: 723 AN: 2108

Alfa AF: 0.226 Hom.: 598

Bravo AF: 0.307

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.60
PhyloP100		-2.1
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: rs560014; hg19: chr13-33625144;