rs480780

Variant names:

• chr13-33033182-G-T
• rs480780
• NM_004795.4:c.819+15923G>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.819+15923G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,104 control chromosomes in the GnomAD database, including 8,360 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 (8360 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.827
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KL	NM_004795.4	MANE Select	c.819+15923G>T		intron	N/A	NP_004786.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KL	ENST00000380099.4	TSL:1 MANE Select	c.819+15923G>T		intron	N/A	ENSP00000369442.3
	KL	ENST00000487852.1	TSL:5	n.827+15923G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46672 AN: 151984 Hom.: 8349 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.307 AC: 46699 AN: 152104 Hom.: 8360 Cov.: 32 AF XY: 0.306 AC XY: 22769 AN XY: 74330

African (AFR) AF: 0.136 AC: 5647 AN: 41502

American (AMR) AF: 0.426 AC: 6514 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1227 AN: 3466

East Asian (EAS) AF: 0.158 AC: 819 AN: 5174

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4822

European-Finnish (FIN) AF: 0.379 AC: 4000 AN: 10558

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26191 AN: 67982

Other (OTH) AF: 0.335 AC: 706 AN: 2106

Alfa AF: 0.331 Hom.: 1213

Bravo AF: 0.306

Asia WGS AF: 0.253 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.83
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: rs480780; hg19: chr13-33607319;