rs687045

chr13-33050752-A-Cchr13-33050752-A-Gchr13-33050752-A-T

Variant summary

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

The NM_004795.4(KL):c.820-3015A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,208 control chromosomes in the GnomAD database, including 9,016 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 0.31 (9016 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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 (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KL	NM_004795.4	c.820-3015A>C		intron_variant		ENST00000380099.4
KL	XM_006719895.3	c.-102-3015A>C		intron_variant
KL	XM_047430775.1	c.820-3015A>C		intron_variant
KL	XM_047430776.1	c.820-3015A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KL	ENST00000380099.4	c.820-3015A>C		intron_variant		1	NM_004795.4	P1
KL	ENST00000487852.1	n.828-3015A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47044 AN: 152090 Hom.: 9005 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.309 AC: 47065 AN: 152208 Hom.: 9016 Cov.: 32 AF XY: 0.309 AC XY: 22970 AN XY: 74406

Gnomad4 AFR AF: 0.0901

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.342

Alfa AF: 0.359 Hom.: 4747

Bravo AF: 0.308

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.2
Dann	Benign	0.73

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: rs687045; hg19: chr13-33624889;