dbSNP rs3745706: FGF21:c.*161C>T (chr19-48758381-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019113.4(FGF21):c.*161C>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
NM_019113.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.281

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 made for transcript

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 rank	MANE	Protein	UniProt
FGF21	NM_019113.4 link	c.*161C>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.*161C>T		downstream_gene_variant		1	NM_019113.4	ENSP00000471477.1		Q9NSA1
FGF21	ENST00000222157.5 link	c.*161C>T		downstream_gene_variant		1		ENSP00000222157.3		Q9NSA1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44612

AN:

151788

Hom.:

7711

Cov.:

show subpopulations

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.:

AF XY:

0.331

AC XY:

91692

AN XY:

277296

show subpopulations

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.:

AF XY:

0.305

AC XY:

22653

AN XY:

74194

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over