rs211235

Variant names:

• chr13-33021062-T-G
• rs211235
• NM_004795.4:c.819+3803T>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.819+3803T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,058 control chromosomes in the GnomAD database, including 17,682 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 0.46 (17682 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.819+3803T>G		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-103+4749T>G		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.819+3803T>G		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.819+3803T>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.819+3803T>G		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.827+3803T>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70281 AN: 151940 Hom.: 17670 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.462 AC: 70317 AN: 152058 Hom.: 17682 Cov.: 32 AF XY: 0.464 AC XY: 34444 AN XY: 74312

African (AFR) AF: 0.295 AC: 12217 AN: 41482

American (AMR) AF: 0.540 AC: 8257 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2100 AN: 3468

East Asian (EAS) AF: 0.161 AC: 835 AN: 5178

South Asian (SAS) AF: 0.411 AC: 1976 AN: 4812

European-Finnish (FIN) AF: 0.573 AC: 6049 AN: 10560

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37270 AN: 67964

Other (OTH) AF: 0.478 AC: 1006 AN: 2106

Alfa AF: 0.496 Hom.: 2476

Bravo AF: 0.453

Asia WGS AF: 0.326 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.1
DANN	Benign	0.75
PhyloP100		0.058
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: rs211235; hg19: chr13-33595200;