rs2516571

Variant names:

• chr13-33041930-G-A
• rs2516571
• NM_004795.4:c.820-11837G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-33041930-G-A
• chr13-33041930-G-C

Variant summary

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

The NM_004795.4(KL):​c.820-11837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,156 control chromosomes in the GnomAD database, including 52,829 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 0.83 (52829 hom., cov: 31)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• Publications: 3 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.856 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.820-11837G>A		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.820-11837G>A		intron	N/A	ENSP00000369442.3	Q9UEF7-1
	KL	ENST00000487852.1	TSL:5	n.828-11837G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126491 AN: 152038 Hom.: 52781 Cov.: 31

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.832 AC: 126594 AN: 152156 Hom.: 52829 Cov.: 31 AF XY: 0.835 AC XY: 62129 AN XY: 74406

African (AFR) AF: 0.770 AC: 31931 AN: 41492

American (AMR) AF: 0.869 AC: 13283 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3149 AN: 3468

East Asian (EAS) AF: 0.764 AC: 3953 AN: 5174

South Asian (SAS) AF: 0.826 AC: 3986 AN: 4828

European-Finnish (FIN) AF: 0.907 AC: 9609 AN: 10598

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57845 AN: 67982

Other (OTH) AF: 0.843 AC: 1783 AN: 2116

Alfa AF: 0.849 Hom.: 91359

Bravo AF: 0.830

Asia WGS AF: 0.788 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.73
PhyloP100		-0.32
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: rs2516571; hg19: chr13-33616067;