rs495764

Variant names:

• chr13-33025945-T-A
• rs495764
• NM_004795.4:c.819+8686T>A

Your query was ambiguous. Multiple possible variants found:

• chr13-33025945-T-A
• chr13-33025945-T-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+8686T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,152 control chromosomes in the GnomAD database, including 43,418 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 0.74 (43418 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.819+8686T>A		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-103+9632T>A		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.819+8686T>A		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.819+8686T>A		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+8686T>A		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.827+8686T>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112210 AN: 152034 Hom.: 43402 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.738 AC: 112264 AN: 152152 Hom.: 43418 Cov.: 32 AF XY: 0.741 AC XY: 55129 AN XY: 74384

African (AFR) AF: 0.491 AC: 20376 AN: 41460

American (AMR) AF: 0.764 AC: 11691 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3113 AN: 3472

East Asian (EAS) AF: 0.635 AC: 3281 AN: 5166

South Asian (SAS) AF: 0.802 AC: 3867 AN: 4820

European-Finnish (FIN) AF: 0.894 AC: 9485 AN: 10606

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57726 AN: 68010

Other (OTH) AF: 0.776 AC: 1642 AN: 2116

Alfa AF: 0.779 Hom.: 5930

Bravo AF: 0.718

Asia WGS AF: 0.713 AC: 2481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.53
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: rs495764; hg19: chr13-33600083;