rs520103

Variant names:

• chr13-33045958-T-A
• rs520103
• NM_004795.4:c.820-7809T>A

Your query was ambiguous. Multiple possible variants found:

• chr13-33045958-T-A
• chr13-33045958-T-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.820-7809T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,204 control chromosomes in the GnomAD database, including 55,483 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 0.85 (55483 hom., cov: 33)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.820-7809T>A		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-7809T>A		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.820-7809T>A		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.820-7809T>A		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.820-7809T>A		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-7809T>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129772 AN: 152086 Hom.: 55434 Cov.: 33

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.853 AC: 129882 AN: 152204 Hom.: 55483 Cov.: 33 AF XY: 0.856 AC XY: 63693 AN XY: 74414

African (AFR) AF: 0.826 AC: 34271 AN: 41504

American (AMR) AF: 0.876 AC: 13400 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3161 AN: 3472

East Asian (EAS) AF: 0.825 AC: 4267 AN: 5174

South Asian (SAS) AF: 0.837 AC: 4035 AN: 4818

European-Finnish (FIN) AF: 0.909 AC: 9640 AN: 10606

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58234 AN: 68014

Other (OTH) AF: 0.857 AC: 1811 AN: 2112

Alfa AF: 0.849 Hom.: 6301

Bravo AF: 0.853

Asia WGS AF: 0.827 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.52
PhyloP100		-0.37
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: rs520103; hg19: chr13-33620095;