chr13-33026095-T-C

Variant names:

• chr13-33026095-T-C
• rs571118
• NM_004795.4:c.819+8836T>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.819+8836T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,102 control chromosomes in the GnomAD database, including 14,052 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 0.42 (14052 hom., cov: 31)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.819+8836T>C		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-103+9782T>C		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.819+8836T>C		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.819+8836T>C		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.819+8836T>C		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.827+8836T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63916 AN: 151984 Hom.: 14049 Cov.: 31

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.420 AC: 63934 AN: 152102 Hom.: 14052 Cov.: 31 AF XY: 0.425 AC XY: 31579 AN XY: 74356

African (AFR) AF: 0.339 AC: 14058 AN: 41462

American (AMR) AF: 0.326 AC: 4994 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2454 AN: 5158

South Asian (SAS) AF: 0.559 AC: 2691 AN: 4816

European-Finnish (FIN) AF: 0.514 AC: 5442 AN: 10578

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30952 AN: 67998

Other (OTH) AF: 0.432 AC: 912 AN: 2110

Alfa AF: 0.437 Hom.: 12626

Bravo AF: 0.401

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.60
PhyloP100		1.4
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: rs571118; hg19: chr13-33600233;