rs522796

Positions:

• chr13-33055918-C-T

Variant summary

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

The NM_004795.4(KL):​c.1599+603C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,080 control chromosomes in the GnomAD database, including 23,056 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 0.54 (23056 hom., cov: 33)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.1599+603C>T		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.678+603C>T		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.1649+553C>T		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.1649+553C>T		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.1599+603C>T		intron_variant		1	NM_004795.4	ENSP00000369442	P1
KL	ENST00000487852.1	n.1657+553C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82569 AN: 151962 Hom.: 23029 Cov.: 33

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.543 AC: 82648 AN: 152080 Hom.: 23056 Cov.: 33 AF XY: 0.541 AC XY: 40231 AN XY: 74352

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.552

Alfa AF: 0.560 Hom.: 10923

Bravo AF: 0.544

Asia WGS AF: 0.366 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.39

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: rs522796; hg19: chr13-33630055;