rs2516571

Positions:

• chr13-33041930-G-A
• chr13-33041930-G-C

Variant summary

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

The NM_004795.4(KL):​c.820-11837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,156 control chromosomes in the GnomAD database, including 52,829 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 0.83 (52829 hom., cov: 31)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.820-11837G>A		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-11837G>A		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.820-11837G>A		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.820-11837G>A		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.820-11837G>A		intron_variant		1	NM_004795.4	ENSP00000369442	P1
KL	ENST00000487852.1	n.828-11837G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126491 AN: 152038 Hom.: 52781 Cov.: 31

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.832 AC: 126594 AN: 152156 Hom.: 52829 Cov.: 31 AF XY: 0.835 AC XY: 62129 AN XY: 74406

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.843

Alfa AF: 0.850 Hom.: 71915

Bravo AF: 0.830

Asia WGS AF: 0.788 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.73

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: rs2516571; hg19: chr13-33616067;