rs3745706

Variant names:

• chr19-48758381-C-T
• rs3745706
• NM_019113.4:c.*161C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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	c.*161C>T		downstream_gene_variant		ENST00000593756.6	NP_061986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF21	ENST00000593756.6	c.*161C>T		downstream_gene_variant		1	NM_019113.4	ENSP00000471477.1
FGF21	ENST00000222157.5	c.*161C>T		downstream_gene_variant		1		ENSP00000222157.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44612 AN: 151788 Hom.: 7711 Cov.: 32

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.: 7 AF XY: 0.331 AC XY: 91692 AN XY: 277296

African (AFR) AF: 0.115 AC: 1382 AN: 11982

American (AMR) AF: 0.359 AC: 4511 AN: 12572

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 4712 AN: 13022

East Asian (EAS) AF: 0.533 AC: 14017 AN: 26292

South Asian (SAS) AF: 0.353 AC: 12204 AN: 34612

European-Finnish (FIN) AF: 0.424 AC: 14236 AN: 33600

Middle Eastern (MID) AF: 0.323 AC: 665 AN: 2060

European-Non Finnish (NFE) AF: 0.309 AC: 117720 AN: 380904

Other (OTH) AF: 0.336 AC: 9349 AN: 27846

GnomAD4 genome AF: 0.294 AC: 44636 AN: 151902 Hom.: 7726 Cov.: 32 AF XY: 0.305 AC XY: 22653 AN XY: 74194

African (AFR) AF: 0.121 AC: 5035 AN: 41462

American (AMR) AF: 0.366 AC: 5587 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1236 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3325 AN: 5166

South Asian (SAS) AF: 0.374 AC: 1799 AN: 4812

European-Finnish (FIN) AF: 0.425 AC: 4460 AN: 10498

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22034 AN: 67918

Other (OTH) AF: 0.327 AC: 690 AN: 2110

Alfa AF: 0.313 Hom.: 2639

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
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3745706; hg19: chr19-49261638;