rs6854452

Variant names:

• chr4-39444717-T-A
• rs6854452
• NM_175737.4:c.1606-1615T>A

Variant summary

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

The NM_175737.4(KLB):​c.1606-1615T>A 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 152,156 control chromosomes in the GnomAD database, including 7,063 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 0.29 (7063 hom., cov: 32)
• Consequence: KLB NM_175737.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 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.1606-1615T>A		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.1606-1615T>A		intron	N/A	ENSP00000257408.4	Q86Z14
	KLB	ENST00000859482.1		c.1606-1642T>A		intron	N/A	ENSP00000529541.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44090 AN: 152038 Hom.: 7055 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.290 AC: 44117 AN: 152156 Hom.: 7063 Cov.: 32 AF XY: 0.297 AC XY: 22107 AN XY: 74382

African (AFR) AF: 0.150 AC: 6224 AN: 41526

American (AMR) AF: 0.369 AC: 5635 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2038 AN: 5172

South Asian (SAS) AF: 0.443 AC: 2134 AN: 4818

European-Finnish (FIN) AF: 0.371 AC: 3918 AN: 10562

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22335 AN: 68000

Other (OTH) AF: 0.275 AC: 582 AN: 2114

Alfa AF: 0.301 Hom.: 913

Bravo AF: 0.281

Asia WGS AF: 0.435 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.64
PhyloP100		-0.080
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: rs6854452; hg19: chr4-39446337;