rs3745706

chr19-48758381-C-T

Variant summary

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

The 19-48758381-C-T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 694,792 control chromosomes in the GnomAD database, including 39,689 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 (7726 hom., cov: 32)
  • Exomes 𝑓: 0.33 (31963 hom.)
• Consequence: FGF21 ENST00000222157.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

Genes affected

FGF21 (HGNC:3678): (fibroblast growth factor 21) Theis gene encodes a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. This protein is a secreted endocrine factor that functions as a major metabolic regulator. The encoded protein stimulates the uptake of glucose in adipose tissue. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF21	ENST00000222157.5			downstream_gene_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44612 AN: 151788 Hom.: 7711 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.329 AC: 178796 AN: 542890 Hom.: 31963 Cov.: 7 AF XY: 0.331 AC XY: 91692 AN XY: 277296

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.294 AC: 44636 AN: 151902 Hom.: 7726 Cov.: 32 AF XY: 0.305 AC XY: 22653 AN XY: 74194

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.327

Alfa AF: 0.312 Hom.: 1537

Bravo AF: 0.283

Asia WGS AF: 0.509 AC: 1768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.8
Dann	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3745706; hg19: chr19-49261638;