rs12152703

Variant names:

• chr4-39420199-G-T
• rs12152703
• NM_175737.4:c.825+12425G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175737.4(KLB):​c.825+12425G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,802 control chromosomes in the GnomAD database, including 6,696 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 (6696 hom., cov: 30)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 8 publications found

Genes affected

KLB (HGNC:15527): (klotho beta) Enables fibroblast growth factor binding activity and fibroblast growth factor receptor binding activity. Predicted to be involved in fibroblast growth factor receptor signaling pathway. Predicted to act upstream of or within positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway and positive regulation of cell population proliferation. Predicted to be located in plasma membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLB	NM_175737.4	c.825+12425G>T		intron_variant	Intron 1 of 4	ENST00000257408.5	NP_783864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLB	ENST00000257408.5	c.825+12425G>T		intron_variant	Intron 1 of 4	1	NM_175737.4	ENSP00000257408.4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42143 AN: 151684 Hom.: 6693 Cov.: 30

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.278 AC: 42155 AN: 151802 Hom.: 6696 Cov.: 30 AF XY: 0.277 AC XY: 20574 AN XY: 74188

African (AFR) AF: 0.437 AC: 18087 AN: 41354

American (AMR) AF: 0.201 AC: 3058 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3466

East Asian (EAS) AF: 0.105 AC: 544 AN: 5170

South Asian (SAS) AF: 0.205 AC: 986 AN: 4808

European-Finnish (FIN) AF: 0.264 AC: 2787 AN: 10550

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15073 AN: 67944

Other (OTH) AF: 0.260 AC: 547 AN: 2102

Alfa AF: 0.257 Hom.: 1233

Bravo AF: 0.280

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		0.0060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12152703; hg19: chr4-39421819;