rs685417

chr13-33038995-G-A

Variant summary

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

The NM_004795.4(KL):c.820-14772G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,914 control chromosomes in the GnomAD database, including 29,119 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 0.60 (29119 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.820-14772G>A		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-102-14772G>A		intron_variant
KL	XM_047430775.1	c.820-14772G>A		intron_variant
KL	XM_047430776.1	c.820-14772G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.820-14772G>A		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.828-14772G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91478 AN: 151796 Hom.: 29108 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.602 AC: 91519 AN: 151914 Hom.: 29119 Cov.: 32 AF XY: 0.605 AC XY: 44921 AN XY: 74260

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.647

Alfa AF: 0.681 Hom.: 40116

Bravo AF: 0.594

Asia WGS AF: 0.654 AC: 2269 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.58
Dann	Benign	0.80

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: rs685417; hg19: chr13-33613132;