rs1207362

Positions:

• chr13-33038702-G-T

Variant summary

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

The NM_004795.4(KL):​c.820-15065G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,968 control chromosomes in the GnomAD database, including 6,603 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 0.28 (6603 hom., cov: 33)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.820-15065G>T		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-102-15065G>T		intron_variant
KL	XM_047430775.1	c.820-15065G>T		intron_variant
KL	XM_047430776.1	c.820-15065G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.820-15065G>T		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.828-15065G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42928 AN: 151850 Hom.: 6600 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.283 AC: 42943 AN: 151968 Hom.: 6603 Cov.: 33 AF XY: 0.286 AC XY: 21241 AN XY: 74266

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.300

Alfa AF: 0.286 Hom.: 782

Bravo AF: 0.274

Asia WGS AF: 0.403 AC: 1397 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.47

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: rs1207362; hg19: chr13-33612839;