chr4-39429349-C-T

Variant names:

• chr4-39429349-C-T
• rs1979283
• NM_175737.4:c.826-4861C>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.826-4861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,004 control chromosomes in the GnomAD database, including 29,861 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 0.61 (29861 hom., cov: 32)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.686
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175737.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLB	NM_175737.4	MANE Select	c.826-4861C>T		intron	N/A	NP_783864.1	Q86Z14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLB	ENST00000257408.5	TSL:1 MANE Select	c.826-4861C>T		intron	N/A	ENSP00000257408.4	Q86Z14
	KLB	ENST00000859482.1		c.826-4861C>T		intron	N/A	ENSP00000529541.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93205 AN: 151884 Hom.: 29843 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.613 AC: 93247 AN: 152004 Hom.: 29861 Cov.: 32 AF XY: 0.617 AC XY: 45834 AN XY: 74280

African (AFR) AF: 0.418 AC: 17292 AN: 41416

American (AMR) AF: 0.717 AC: 10959 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2138 AN: 3470

East Asian (EAS) AF: 0.712 AC: 3676 AN: 5162

South Asian (SAS) AF: 0.675 AC: 3253 AN: 4818

European-Finnish (FIN) AF: 0.718 AC: 7605 AN: 10586

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 46038 AN: 67960

Other (OTH) AF: 0.636 AC: 1342 AN: 2110

Alfa AF: 0.655 Hom.: 130158

Bravo AF: 0.605

Asia WGS AF: 0.669 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.43
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1979283; hg19: chr4-39430969;