rs9596717

chr13-33057870-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.1599+2555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 152,244 control chromosomes in the GnomAD database, including 361 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 0.068 (361 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.1599+2555A>G		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.678+2555A>G		intron_variant
KL	XM_047430775.1	c.1650-78A>G		intron_variant
KL	XM_047430776.1	c.1649+2505A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.1599+2555A>G		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.1657+2505A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10397 AN: 152126 Hom.: 359 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.0731

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

GnomAD4 genome AF: 0.0684 AC: 10411 AN: 152244 Hom.: 361 Cov.: 32 AF XY: 0.0681 AC XY: 5071 AN XY: 74428

Gnomad4 AFR AF: 0.0573

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0856

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0558

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0721 Hom.: 61

Bravo AF: 0.0658

Asia WGS AF: 0.0310 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.89
Dann	Benign	0.77

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: rs9596717; hg19: chr13-33632007;