rs9536313

Variant names:

• chr13-33053721-C-G
• rs9536313
• NM_004795.4:c.820-46C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-33053721-C-G
• chr13-33053721-C-A
• chr13-33053721-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004795.4(KL):​c.820-46C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,580,028 control chromosomes in the GnomAD database, including 20,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1942 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18108 hom.)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.323
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-33053721-C-G is Benign according to our data. Variant chr13-33053721-C-G is described in ClinVar as Benign. ClinVar VariationId is 1181821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 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.820-46C>G		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.820-46C>G		intron	N/A	ENSP00000369442.3	Q9UEF7-1
	KL	ENST00000487852.1	TSL:5	n.828-46C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23701 AN: 152056 Hom.: 1941 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.141 AC: 35039 AN: 248784 AF XY: 0.146

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.0734

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.00114

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.154 AC: 220192 AN: 1427854 Hom.: 18108 Cov.: 28 AF XY: 0.155 AC XY: 110347 AN XY: 712302

African (AFR) AF: 0.178 AC: 5845 AN: 32768

American (AMR) AF: 0.0768 AC: 3425 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 5397 AN: 25876

East Asian (EAS) AF: 0.000861 AC: 34 AN: 39508

South Asian (SAS) AF: 0.174 AC: 14837 AN: 85204

European-Finnish (FIN) AF: 0.198 AC: 10507 AN: 53094

Middle Eastern (MID) AF: 0.163 AC: 934 AN: 5726

European-Non Finnish (NFE) AF: 0.157 AC: 169452 AN: 1081924

Other (OTH) AF: 0.165 AC: 9761 AN: 59182

GnomAD4 genome AF: 0.156 AC: 23714 AN: 152174 Hom.: 1942 Cov.: 32 AF XY: 0.157 AC XY: 11677 AN XY: 74394

African (AFR) AF: 0.183 AC: 7590 AN: 41500

American (AMR) AF: 0.103 AC: 1573 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.162 AC: 777 AN: 4806

European-Finnish (FIN) AF: 0.193 AC: 2041 AN: 10598

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

European-Non Finnish (NFE) AF: 0.155 AC: 10526 AN: 68004

Other (OTH) AF: 0.147 AC: 311 AN: 2114

Alfa AF: 0.107 Hom.: 237

Bravo AF: 0.148

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.92
DANN	Benign	0.41
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: rs9536313; hg19: chr13-33627858;