rs480780

chr13-33033182-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.819+15923G>T		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-103+16869G>T		intron_variant
KL	XM_047430775.1	c.819+15923G>T		intron_variant
KL	XM_047430776.1	c.819+15923G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.819+15923G>T		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.827+15923G>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.335

Alfa AF: 0.338 Hom.: 1205

Bravo AF: 0.306

Asia WGS AF: 0.253 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	11
Dann	Benign	0.83

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: rs480780; hg19: chr13-33607319;