rs7670903

Positions:

• chr4-39441340-A-G

Variant summary

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

The NM_175737.4(KLB):​c.1605+3345A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,934 control chromosomes in the GnomAD database, including 25,484 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 0.58 (25484 hom., cov: 31)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLB	NM_175737.4	c.1605+3345A>G		intron_variant		ENST00000257408.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLB	ENST00000257408.5	c.1605+3345A>G		intron_variant		1	NM_175737.4	P1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87457 AN: 151814 Hom.: 25463 Cov.: 31

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.576 AC: 87517 AN: 151934 Hom.: 25484 Cov.: 31 AF XY: 0.580 AC XY: 43064 AN XY: 74254

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.550

Alfa AF: 0.597 Hom.: 14447

Bravo AF: 0.564

Asia WGS AF: 0.548 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.63

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: rs7670903; hg19: chr4-39442960;