rs2238166

Positions:

• chr13-33020543-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.819+3284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,828 control chromosomes in the GnomAD database, including 8,357 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 (8357 hom., cov: 31)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.819+3284C>T		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-103+4230C>T		intron_variant
KL	XM_047430775.1	c.819+3284C>T		intron_variant
KL	XM_047430776.1	c.819+3284C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.819+3284C>T		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.827+3284C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.310 AC: 46980 AN: 151710 Hom.: 8347 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.310 AC: 47003 AN: 151828 Hom.: 8357 Cov.: 31 AF XY: 0.308 AC XY: 22873 AN XY: 74194

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.339

Alfa AF: 0.337 Hom.: 1174

Bravo AF: 0.313

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.029
DANN	Benign	0.74

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: rs2238166; hg19: chr13-33594681;