rs687045

Variant names:

• chr13-33050752-A-C
• rs687045
• NM_004795.4:c.820-3015A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-33050752-A-C
• chr13-33050752-A-G
• chr13-33050752-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004795.4(KL):​c.820-3015A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,208 control chromosomes in the GnomAD database, including 9,016 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 0.31 (9016 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 6 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KL	NM_004795.4	MANE Select	c.820-3015A>C		intron	N/A	NP_004786.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KL	ENST00000380099.4	TSL:1 MANE Select	c.820-3015A>C		intron	N/A	ENSP00000369442.3	Q9UEF7-1
	KL	ENST00000487852.1	TSL:5	n.828-3015A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47044 AN: 152090 Hom.: 9005 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.309 AC: 47065 AN: 152208 Hom.: 9016 Cov.: 32 AF XY: 0.309 AC XY: 22970 AN XY: 74406

African (AFR) AF: 0.0901 AC: 3743 AN: 41564

American (AMR) AF: 0.451 AC: 6899 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1450 AN: 3468

East Asian (EAS) AF: 0.169 AC: 872 AN: 5172

South Asian (SAS) AF: 0.305 AC: 1469 AN: 4814

European-Finnish (FIN) AF: 0.381 AC: 4040 AN: 10590

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27366 AN: 67988

Other (OTH) AF: 0.342 AC: 724 AN: 2116

Alfa AF: 0.362 Hom.: 5344

Bravo AF: 0.308

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.73
PhyloP100		0.033
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: rs687045; hg19: chr13-33624889;