13-33025521-A-G

Variant names:

• chr13-33025521-A-G
• rs565587
• NM_004795.4:c.819+8262A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004795.4(KL):​c.819+8262A>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 152,006 control chromosomes in the GnomAD database, including 28,293 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 (28293 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.819+8262A>G		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-103+9208A>G		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.819+8262A>G		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.819+8262A>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+8262A>G		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.827+8262A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89562 AN: 151888 Hom.: 28284 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.660

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: 0.635

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

GnomAD4 genome AF: 0.589 AC: 89598 AN: 152006 Hom.: 28293 Cov.: 32 AF XY: 0.592 AC XY: 43967 AN XY: 74330

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.635

Alfa AF: 0.591 Hom.: 4036

Bravo AF: 0.580

Asia WGS AF: 0.636 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.8
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs565587; hg19: chr13-33599659;