rs385564

Positions:

• chr13-33018271-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.819+1012C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,078 control chromosomes in the GnomAD database, including 6,641 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 0.29 (6641 hom., cov: 33)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.819+1012C>G		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-103+1958C>G		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.819+1012C>G		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.819+1012C>G		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.819+1012C>G		intron_variant		1	NM_004795.4	ENSP00000369442	P1
KL	ENST00000487852.1	n.827+1012C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44567 AN: 151958 Hom.: 6635 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.293 AC: 44589 AN: 152078 Hom.: 6641 Cov.: 33 AF XY: 0.293 AC XY: 21794 AN XY: 74334

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.304

Alfa AF: 0.306 Hom.: 997

Bravo AF: 0.292

Asia WGS AF: 0.269 AC: 934 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	9.4
DANN	Benign	0.46

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: rs385564; hg19: chr13-33592409;