rs1207568

Variant names:

• chr13-33016046-G-A
• rs1207568
• XM_047430819.1:c.397C>T

Variant summary

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

The XM_047430819.1(LOC124903151):​c.397C>T​(p.Pro133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,232 control chromosomes in the GnomAD database, including 2,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2381 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: LOC124903151 XM_047430819.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

Genes affected

LOC124903151 (HGNC:):

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903151	XM_047430819.1	c.397C>T	p.Pro133Ser	missense_variant	Exon 1 of 2		XP_047286775.1
KL	XM_006719895.3	c.-370G>A		upstream_gene_variant			XP_006719958.1
LOC124903151	XR_007063749.1	n.-32C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25965 AN: 152114 Hom.: 2377 Cov.: 33

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.167

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.171 AC: 25972 AN: 152232 Hom.: 2381 Cov.: 33 AF XY: 0.172 AC XY: 12832 AN XY: 74414

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.165

Alfa AF: 0.178 Hom.: 507

Bravo AF: 0.168

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.6
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1207568; hg19: chr13-33590184;