Genetic Variant FGF19:c.*692T>C (chr11-69698570-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005117.3(FGF19):c.*692T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 191,524 control chromosomes in the GnomAD database, including 11,762 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 0.34 ( 9275 hom., cov: 33)

Exomes 𝑓: 0.34 ( 2487 hom. )

Consequence

FGF19
NM_005117.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.82

Publications

18 publications found

Variant links:

Genes affected

FGF19 (HGNC:3675): (fibroblast growth factor 19) The protein encoded by this gene is 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 including embryonic development cell growth, morphogenesis, tissue repair, tumor growth and invasion. This growth factor is a high affinity, heparin dependent ligand for FGFR4. Expression of this gene was detected only in fetal but not adult brain tissue. Synergistic interaction of the chick homolog and Wnt-8c has been shown to be required for initiation of inner ear development. [provided by RefSeq, Jul 2008]

FGF19 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=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF19	NM_005117.3 link	c.*692T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000294312.4	NP_005108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF19	ENST00000294312.4 link	c.*692T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_005117.3	ENSP00000294312.3

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52038

AN:

151888

Hom.:

9273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.353

GnomAD4 exome

AF:

0.342

AC:

13522

AN:

39518

Hom.:

2487

Cov.:

AF XY:

0.341

AC XY:

6269

AN XY:

18362

show subpopulations

African (AFR)

AF:

0.405

AC:

620

AN:

1532

American (AMR)

AF:

0.282

AC:

270

AN:

956

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

793

AN:

2534

East Asian (EAS)

AF:

0.508

AC:

3552

AN:

6986

South Asian (SAS)

AF:

0.506

AC:

167

AN:

330

European-Finnish (FIN)

AF:

0.404

AC:

AN:

Middle Eastern (MID)

AF:

0.417

AC:

101

AN:

242

European-Non Finnish (NFE)

AF:

0.294

AC:

6947

AN:

23660

Other (OTH)

AF:

0.326

AC:

1051

AN:

3226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

430

860

1289

1719

2149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.342

AC:

52050

AN:

152006

Hom.:

9275

Cov.:

AF XY:

0.348

AC XY:

25893

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.403

AC:

16721

AN:

41470

American (AMR)

AF:

0.263

AC:

4020

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1198

AN:

3470

East Asian (EAS)

AF:

0.513

AC:

2627

AN:

5118

South Asian (SAS)

AF:

0.477

AC:

2299

AN:

4824

European-Finnish (FIN)

AF:

0.388

AC:

4098

AN:

10570

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20063

AN:

67956

Other (OTH)

AF:

0.350

AC:

739

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1751

3501

5252

7002

8753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.315

Hom.:

16073

Bravo

AF:

0.335

Asia WGS

AF:

0.458

AC:

1587

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.15

(source)

DANN

Benign

0.49

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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