rs2283368

Positions:

• chr13-33019132-T-C

Variant summary

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

The NM_004795.4(KL):​c.819+1873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,148 control chromosomes in the GnomAD database, including 1,835 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 0.15 (1835 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.819+1873T>C		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-103+2819T>C		intron_variant
KL	XM_047430775.1	c.819+1873T>C		intron_variant
KL	XM_047430776.1	c.819+1873T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.819+1873T>C		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.827+1873T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22385 AN: 152030 Hom.: 1833 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.147 AC: 22402 AN: 152148 Hom.: 1835 Cov.: 32 AF XY: 0.152 AC XY: 11302 AN XY: 74362

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0918

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.134

Alfa AF: 0.132 Hom.: 1196

Bravo AF: 0.139

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.7
DANN	Benign	0.81

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: rs2283368; hg19: chr13-33593270;