Genetic Variant FGF21:c.*206G>C (chr19-48758426-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019113.4(FGF21):c.*206G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000033 in 302,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

FGF21
NM_019113.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

0 publications found

Variant links:

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]

FGF21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF21	NM_019113.4 link	c.*206G>C		downstream_gene_variant		ENST00000593756.6	NP_061986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF21	ENST00000593756.6 link	c.*206G>C		downstream_gene_variant		1	NM_019113.4	ENSP00000471477.1
FGF21	ENST00000222157.5 link	c.*206G>C		downstream_gene_variant		1		ENSP00000222157.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000330

AC:

AN:

302728

Hom.:

AF XY:

0.00

AC XY:

AN XY:

155688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7568

American (AMR)

AF:

0.00

AC:

AN:

9864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10078

East Asian (EAS)

AF:

0.00

AC:

AN:

23058

South Asian (SAS)

AF:

0.00

AC:

AN:

13260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1446

European-Non Finnish (NFE)

AF:

0.00000512

AC:

AN:

195394

Other (OTH)

AF:

0.00

AC:

AN:

18648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.14

(source)

DANN

Benign

0.21

PhyloP100

-1.9

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over