NM_004795.4:c.819+7801A>G

Variant names:

• chr13-33025060-A-G
• rs525014
• NM_004795.4:c.819+7801A>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+7801A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,996 control chromosomes in the GnomAD database, including 28,286 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 0.59 (28286 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KL	NM_004795.4	MANE Select	c.819+7801A>G		intron	N/A	NP_004786.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KL	ENST00000380099.4	TSL:1 MANE Select	c.819+7801A>G		intron	N/A	ENSP00000369442.3
	KL	ENST00000487852.1	TSL:5	n.827+7801A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89546 AN: 151878 Hom.: 28275 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.589 AC: 89584 AN: 151996 Hom.: 28286 Cov.: 32 AF XY: 0.592 AC XY: 43964 AN XY: 74308

African (AFR) AF: 0.338 AC: 14001 AN: 41426

American (AMR) AF: 0.663 AC: 10126 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2285 AN: 3468

East Asian (EAS) AF: 0.635 AC: 3279 AN: 5166

South Asian (SAS) AF: 0.632 AC: 3049 AN: 4822

European-Finnish (FIN) AF: 0.701 AC: 7404 AN: 10558

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47150 AN: 67970

Other (OTH) AF: 0.638 AC: 1344 AN: 2108

Alfa AF: 0.664 Hom.: 132085

Bravo AF: 0.580

Asia WGS AF: 0.637 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.86
PhyloP100		1.2
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: rs525014; hg19: chr13-33599198;