rs1207362

Variant names:

• chr13-33038702-G-T
• rs1207362
• NM_004795.4:c.820-15065G>T

Variant summary

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

The NM_004795.4(KL):​c.820-15065G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,968 control chromosomes in the GnomAD database, including 6,603 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 0.28 (6603 hom., cov: 33)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.820-15065G>T		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-15065G>T		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.820-15065G>T		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.820-15065G>T		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.820-15065G>T		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-15065G>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42928 AN: 151850 Hom.: 6600 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.283 AC: 42943 AN: 151968 Hom.: 6603 Cov.: 33 AF XY: 0.286 AC XY: 21241 AN XY: 74266

African (AFR) AF: 0.215 AC: 8922 AN: 41440

American (AMR) AF: 0.229 AC: 3504 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2694 AN: 5166

South Asian (SAS) AF: 0.396 AC: 1912 AN: 4826

European-Finnish (FIN) AF: 0.320 AC: 3374 AN: 10528

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20419 AN: 67948

Other (OTH) AF: 0.300 AC: 634 AN: 2112

Alfa AF: 0.282 Hom.: 797

Bravo AF: 0.274

Asia WGS AF: 0.403 AC: 1397 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.47
PhyloP100		0.24
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: rs1207362; hg19: chr13-33612839;