rs1334928

Variant names:

• chr13-33041811-T-G
• rs1334928
• NM_004795.4:c.820-11956T>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.820-11956T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,998 control chromosomes in the GnomAD database, including 8,697 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 0.31 (8697 hom., cov: 30)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

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 (AMR) allele frequency at 95% confidence interval = 0.436 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.820-11956T>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.820-11956T>G		intron	N/A	ENSP00000369442.3	Q9UEF7-1
	KL	ENST00000487852.1	TSL:5	n.828-11956T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47499 AN: 151880 Hom.: 8687 Cov.: 30

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.313 AC: 47526 AN: 151998 Hom.: 8697 Cov.: 30 AF XY: 0.312 AC XY: 23172 AN XY: 74304

African (AFR) AF: 0.133 AC: 5525 AN: 41490

American (AMR) AF: 0.445 AC: 6792 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1271 AN: 3470

East Asian (EAS) AF: 0.175 AC: 905 AN: 5164

South Asian (SAS) AF: 0.240 AC: 1158 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4009 AN: 10534

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26715 AN: 67944

Other (OTH) AF: 0.341 AC: 718 AN: 2108

Alfa AF: 0.374 Hom.: 8635

Bravo AF: 0.314

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.54
PhyloP100		0.0090
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: rs1334928; hg19: chr13-33615948;