19-48756272-A-G

Position:

• chr19-48756272-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_019113.4(FGF21):​c.36A>G​(p.Gly12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,613,498 control chromosomes in the GnomAD database, including 298,436 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 0.64 (32197 hom., cov: 31)
  • Exomes 𝑓: 0.59 (266239 hom.)
• Consequence: FGF21 NM_019113.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.114 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF21	NM_019113.4	c.36A>G	p.Gly12=	synonymous_variant	2/4	ENST00000593756.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF21	ENST00000593756.6	c.36A>G	p.Gly12=	synonymous_variant	2/4	1	NM_019113.4	P1
FGF21	ENST00000222157.5	c.36A>G	p.Gly12=	synonymous_variant	1/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97574 AN: 151876 Hom.: 32158 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.627

GnomAD3 exomes AF: 0.666 AC: 166889 AN: 250524 Hom.: 57927 AF XY: 0.660 AC XY: 89463 AN XY: 135492

Gnomad AFR exome AF: 0.706

Gnomad AMR exome AF: 0.784

Gnomad ASJ exome AF: 0.551

Gnomad EAS exome AF: 0.995

Gnomad SAS exome AF: 0.765

Gnomad FIN exome AF: 0.620

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.626

GnomAD4 exome AF: 0.595 AC: 869298 AN: 1461502 Hom.: 266239 Cov.: 61 AF XY: 0.599 AC XY: 435703 AN XY: 727054

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.993

Gnomad4 SAS exome AF: 0.755

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.643 AC: 97669 AN: 151996 Hom.: 32197 Cov.: 31 AF XY: 0.651 AC XY: 48350 AN XY: 74278

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.633

Alfa AF: 0.576 Hom.: 20667

Bravo AF: 0.648

Asia WGS AF: 0.890 AC: 3093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.2
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs838133; hg19: chr19-49259529; COSMIC: COSV55810289; COSMIC: COSV55810289;