rs9527032

Variant names:

• chr13-33056892-G-C
• rs9527032
• NM_004795.4:c.1599+1577G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-33056892-G-C
• chr13-33056892-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.1599+1577G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,014 control chromosomes in the GnomAD database, including 2,003 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 0.16 (2003 hom., cov: 31)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.1599+1577G>C		intron_variant	Intron 3 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.678+1577G>C		intron_variant	Intron 3 of 4		XP_006719958.1
KL	XM_047430775.1	c.1650-1056G>C		intron_variant	Intron 3 of 3		XP_047286731.1
KL	XM_047430776.1	c.1649+1527G>C		intron_variant	Intron 3 of 3		XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.1599+1577G>C		intron_variant	Intron 3 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.1657+1527G>C		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24032 AN: 151896 Hom.: 2001 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.158 AC: 24049 AN: 152014 Hom.: 2003 Cov.: 31 AF XY: 0.159 AC XY: 11839 AN XY: 74286

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0504 Hom.: 61

Bravo AF: 0.150

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.29

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: rs9527032; hg19: chr13-33631029;