rs9526984

chr13-33035800-A-G

Variant summary

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

The NM_004795.4(KL):c.820-17967A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 152,262 control chromosomes in the GnomAD database, including 299 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 0.055 (299 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.820-17967A>G		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-102-17967A>G		intron_variant
KL	XM_047430775.1	c.820-17967A>G		intron_variant
KL	XM_047430776.1	c.820-17967A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.820-17967A>G		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.828-17967A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8410 AN: 152144 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0810

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0599

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

GnomAD4 genome AF: 0.0552 AC: 8412 AN: 152262 Hom.: 299 Cov.: 32 AF XY: 0.0553 AC XY: 4115 AN XY: 74452

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0499

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0576

Gnomad4 FIN AF: 0.0810

Gnomad4 NFE AF: 0.0802

Gnomad4 OTH AF: 0.0593

Alfa AF: 0.0754 Hom.: 480

Bravo AF: 0.0510

Asia WGS AF: 0.0290 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.2
Dann	Benign	0.28

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: rs9526984; hg19: chr13-33609937;