rs567170

chr13-33043649-C-G

Variant summary

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

The NM_004795.4(KL):c.820-10118C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,012 control chromosomes in the GnomAD database, including 9,110 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 0.32 (9110 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.820-10118C>G		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-102-10118C>G		intron_variant
KL	XM_047430775.1	c.820-10118C>G		intron_variant
KL	XM_047430776.1	c.820-10118C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.820-10118C>G		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.828-10118C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48633 AN: 151894 Hom.: 9100 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.320 AC: 48658 AN: 152012 Hom.: 9110 Cov.: 32 AF XY: 0.320 AC XY: 23787 AN XY: 74316

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.347

Alfa AF: 0.350 Hom.: 1304

Bravo AF: 0.320

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.94
Dann	Benign	0.76

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: rs567170; hg19: chr13-33617786;