rs9526983

Variant names:

• chr13-33035145-A-G
• rs9526983
• NM_004795.4:c.819+17886A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-33035145-A-G
• chr13-33035145-A-T

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+17886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 152,278 control chromosomes in the GnomAD database, including 323 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 0.057 (323 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.081 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.819+17886A>G		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-18622A>G		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.819+17886A>G		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.819+17886A>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+17886A>G		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.827+17886A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8745 AN: 152160 Hom.: 322 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0574 AC: 8747 AN: 152278 Hom.: 323 Cov.: 32 AF XY: 0.0579 AC XY: 4308 AN XY: 74466

African (AFR) AF: 0.0140 AC: 584 AN: 41570

American (AMR) AF: 0.0505 AC: 772 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0585 AC: 282 AN: 4822

European-Finnish (FIN) AF: 0.0909 AC: 964 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0829 AC: 5635 AN: 68010

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0376 Hom.: 31

Bravo AF: 0.0523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.094
DANN	Benign	0.38
PhyloP100		-1.1
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: rs9526983; hg19: chr13-33609282;