rs567170

Variant names:

• chr13-33043649-C-G
• rs567170
• NM_004795.4:c.820-10118C>G

Variant summary

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

The NM_004795.4(KL):​c.820-10118C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,012 control chromosomes in the GnomAD database, including 9,110 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 0.32 (9110 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.820-10118C>G		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-10118C>G		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.820-10118C>G		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.820-10118C>G		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.820-10118C>G		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-10118C>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48633 AN: 151894 Hom.: 9100 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.320 AC: 48658 AN: 152012 Hom.: 9110 Cov.: 32 AF XY: 0.320 AC XY: 23787 AN XY: 74316

African (AFR) AF: 0.134 AC: 5544 AN: 41468

American (AMR) AF: 0.450 AC: 6878 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1391 AN: 3458

East Asian (EAS) AF: 0.174 AC: 900 AN: 5172

South Asian (SAS) AF: 0.301 AC: 1442 AN: 4796

European-Finnish (FIN) AF: 0.383 AC: 4042 AN: 10562

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27230 AN: 67962

Other (OTH) AF: 0.347 AC: 732 AN: 2112

Alfa AF: 0.350 Hom.: 1304

Bravo AF: 0.320

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.76
PhyloP100		-0.78
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: rs567170; hg19: chr13-33617786;