13-33053556-G-A

Variant names:

• chr13-33053556-G-A
• rs9527024
• NM_004795.4:c.820-211G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004795.4(KL):​c.820-211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,178 control chromosomes in the GnomAD database, including 1,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1950 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.67
• 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: AR, Unknown Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 13-33053556-G-A is Benign according to our data. Variant chr13-33053556-G-A is described in ClinVar as Benign. ClinVar VariationId is 1288084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.820-211G>A		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-211G>A		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.820-211G>A		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.820-211G>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.820-211G>A		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-211G>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23720 AN: 152060 Hom.: 1949 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.156 AC: 23733 AN: 152178 Hom.: 1950 Cov.: 32 AF XY: 0.157 AC XY: 11685 AN XY: 74406

African (AFR) AF: 0.183 AC: 7607 AN: 41512

American (AMR) AF: 0.103 AC: 1571 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.162 AC: 782 AN: 4826

European-Finnish (FIN) AF: 0.192 AC: 2037 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10529 AN: 67990

Other (OTH) AF: 0.147 AC: 311 AN: 2110

Alfa AF: 0.148 Hom.: 5073

Bravo AF: 0.148

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.4
DANN	Benign	0.54
PhyloP100		2.7
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: rs9527024; hg19: chr13-33627693;