rs7670903

Variant names:

• chr4-39441340-A-G
• rs7670903
• NM_175737.4:c.1605+3345A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 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.1605+3345A>G		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.1605+3345A>G		intron	N/A	ENSP00000257408.4	Q86Z14
	KLB	ENST00000859482.1		c.1605+3345A>G		intron	N/A	ENSP00000529541.1

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

African (AFR) AF: 0.523 AC: 21668 AN: 41414

American (AMR) AF: 0.556 AC: 8477 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1764 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2469 AN: 5172

South Asian (SAS) AF: 0.582 AC: 2806 AN: 4822

European-Finnish (FIN) AF: 0.667 AC: 7029 AN: 10544

Middle Eastern (MID) AF: 0.541 AC: 157 AN: 290

European-Non Finnish (NFE) AF: 0.611 AC: 41503 AN: 67948

Other (OTH) AF: 0.550 AC: 1160 AN: 2108

Alfa AF: 0.597 Hom.: 15944

Bravo AF: 0.564

Asia WGS AF: 0.548 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		-0.79
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: rs7670903; hg19: chr4-39442960;