Genetic Variant FGF21:c.*224C>T (chr19-48758444-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019113.4(FGF21):c.*224C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 409,302 control chromosomes in the GnomAD database, including 2,801 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 0.072 ( 640 hom., cov: 31)

Exomes 𝑓: 0.071 ( 2161 hom. )

Consequence

FGF21
NM_019113.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.740

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF21	NM_019113.4 link	c.*224C>T		downstream_gene_variant		ENST00000593756.6	NP_061986.1	Q9NSA1A0A7U3L5M7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF21	ENST00000593756.6 link	c.*224C>T		downstream_gene_variant		1	NM_019113.4	ENSP00000471477.1		Q9NSA1
FGF21	ENST00000222157.5 link	c.*224C>T		downstream_gene_variant		1		ENSP00000222157.3		Q9NSA1

Frequencies

GnomAD3 genomes

AF:

0.0723

AC:

10855

AN:

150144

Hom.:

637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.0752

Gnomad AMR

AF:

0.0898

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0335

Gnomad OTH

AF:

0.0611

GnomAD4 exome

AF:

0.0713

AC:

18462

AN:

259054

Hom.:

2161

AF XY:

0.0698

AC XY:

9254

AN XY:

132650

show subpopulations

African (AFR)

AF:

0.120

AC:

853

AN:

7108

American (AMR)

AF:

0.0931

AC:

798

AN:

8574

Ashkenazi Jewish (ASJ)

AF:

0.0203

AC:

190

AN:

9374

East Asian (EAS)

AF:

0.408

AC:

9010

AN:

22090

South Asian (SAS)

AF:

0.108

AC:

656

AN:

6096

European-Finnish (FIN)

AF:

0.0231

AC:

472

AN:

20428

Middle Eastern (MID)

AF:

0.0334

AC:

AN:

1318

European-Non Finnish (NFE)

AF:

0.0326

AC:

5457

AN:

167302

Other (OTH)

AF:

0.0586

AC:

982

AN:

16764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

678

1356

2035

2713

3391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0724

AC:

10876

AN:

150248

Hom.:

640

Cov.:

AF XY:

0.0746

AC XY:

5469

AN XY:

73356

show subpopulations

African (AFR)

AF:

0.117

AC:

4752

AN:

40774

American (AMR)

AF:

0.0898

AC:

1345

AN:

14976

Ashkenazi Jewish (ASJ)

AF:

0.0254

AC:

AN:

3458

East Asian (EAS)

AF:

0.277

AC:

1388

AN:

5018

South Asian (SAS)

AF:

0.116

AC:

549

AN:

4726

European-Finnish (FIN)

AF:

0.0273

AC:

281

AN:

10284

Middle Eastern (MID)

AF:

0.0379

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0335

AC:

2266

AN:

67734

Other (OTH)

AF:

0.0614

AC:

128

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

457

914

1370

1827

2284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0537

Hom.:

745

Bravo

AF:

0.0796

Asia WGS

AF:

0.205

AC:

710

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.4

(source)

DANN

Benign

0.82

PhyloP100

0.74

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over