rs9527023

Positions:

• chr13-33053321-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.820-446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,174 control chromosomes in the GnomAD database, including 1,935 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 0.16 (1935 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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]

KL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.820-446T>C		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-446T>C		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.820-446T>C		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.820-446T>C		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.820-446T>C		intron_variant		1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-446T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23689 AN: 152056 Hom.: 1934 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.156 AC: 23702 AN: 152174 Hom.: 1935 Cov.: 32 AF XY: 0.157 AC XY: 11669 AN XY: 74396

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.148

Alfa AF: 0.149 Hom.: 311

Bravo AF: 0.148

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.57

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: rs9527023; hg19: chr13-33627458;