rs1888057

chr13-33048558-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.820-5209C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,270 control chromosomes in the GnomAD database, including 2,866 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 0.18 (2866 hom., cov: 33)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.820-5209C>T		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-102-5209C>T		intron_variant
KL	XM_047430775.1	c.820-5209C>T		intron_variant
KL	XM_047430776.1	c.820-5209C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.820-5209C>T		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.828-5209C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28126 AN: 152152 Hom.: 2866 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.185 AC: 28122 AN: 152270 Hom.: 2866 Cov.: 33 AF XY: 0.187 AC XY: 13886 AN XY: 74446

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.178

Alfa AF: 0.209 Hom.: 1851

Bravo AF: 0.170

Asia WGS AF: 0.259 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.3
Dann	Benign	0.79

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: rs1888057; hg19: chr13-33622695; COSMIC: COSV66309895;