rs495392

Positions:

• chr13-33018055-C-A

Variant summary

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

The NM_004795.4(KL):​c.819+796C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,104 control chromosomes in the GnomAD database, including 4,887 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 0.24 (4887 hom., cov: 33)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.819+796C>A		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-103+1742C>A		intron_variant
KL	XM_047430775.1	c.819+796C>A		intron_variant
KL	XM_047430776.1	c.819+796C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.819+796C>A		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.827+796C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36553 AN: 151986 Hom.: 4877 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.240 AC: 36577 AN: 152104 Hom.: 4887 Cov.: 33 AF XY: 0.241 AC XY: 17948 AN XY: 74326

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.251

Alfa AF: 0.274 Hom.: 7756

Bravo AF: 0.239

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
DANN	Benign	0.33

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: rs495392; hg19: chr13-33592193;