rs9526992

Positions:

• chr13-33039066-G-A

Variant summary

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

The ENST00000380099.4(KL):​c.820-14701G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,046 control chromosomes in the GnomAD database, including 2,489 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 0.17 (2489 hom., cov: 32)
• Consequence: KL ENST00000380099.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.820-14701G>A		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-14701G>A		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.820-14701G>A		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.820-14701G>A		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.820-14701G>A		intron_variant		1	NM_004795.4	ENSP00000369442	P1
KL	ENST00000487852.1	n.828-14701G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26447 AN: 151928 Hom.: 2482 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.174 AC: 26472 AN: 152046 Hom.: 2489 Cov.: 32 AF XY: 0.173 AC XY: 12883 AN XY: 74328

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.157

Alfa AF: 0.170 Hom.: 286

Bravo AF: 0.169

Asia WGS AF: 0.0750 AC: 259 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.020
DANN	Benign	0.44

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: rs9526992; hg19: chr13-33613203;