rs385564

Variant names:

• chr13-33018271-C-G
• rs385564
• NM_004795.4:c.819+1012C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

KL Gene-Disease associations (from GenCC):

• tumoral calcinosis, hyperphosphatemic, familial, 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• tumoral calcinosis, hyperphosphatemic, familial, 3

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KL	NM_004795.4	c.819+1012C>G		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-103+1958C>G		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.819+1012C>G		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.819+1012C>G		intron_variant	Intron 1 of 3		XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.819+1012C>G		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.827+1012C>G		intron_variant	Intron 1 of 4	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

African (AFR) AF: 0.260 AC: 10762 AN: 41462

American (AMR) AF: 0.281 AC: 4294 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1333 AN: 3464

East Asian (EAS) AF: 0.272 AC: 1406 AN: 5178

South Asian (SAS) AF: 0.284 AC: 1371 AN: 4826

European-Finnish (FIN) AF: 0.296 AC: 3124 AN: 10558

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21218 AN: 67978

Other (OTH) AF: 0.304 AC: 641 AN: 2112

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
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs385564; hg19: chr13-33592409;