chr13-33053623-A-G

Position:

• chr13-33053623-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004795.4(KL):​c.820-144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 774,990 control chromosomes in the GnomAD database, including 33,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5842 hom., cov: 33)
  • Exomes 𝑓: 0.30 (28122 hom.)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.08

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]

KL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-33053623-A-G is Benign according to our data. Variant chr13-33053623-A-G is described in ClinVar as [Benign]. Clinvar id is 1233548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KL	NM_004795.4	c.820-144A>G		intron_variant		ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-102-144A>G		intron_variant			XP_006719958.1
KL	XM_047430775.1	c.820-144A>G		intron_variant			XP_047286731.1
KL	XM_047430776.1	c.820-144A>G		intron_variant			XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4	c.820-144A>G		intron_variant		1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.828-144A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40403 AN: 151994 Hom.: 5838 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.295 AC: 183967 AN: 622880 Hom.: 28122 AF XY: 0.296 AC XY: 96030 AN XY: 324506

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.266 AC: 40420 AN: 152110 Hom.: 5842 Cov.: 33 AF XY: 0.268 AC XY: 19904 AN XY: 74368

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.283

Alfa AF: 0.265 Hom.: 781

Bravo AF: 0.257

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.54

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: rs7323281; hg19: chr13-33627760;