chr19-48758444-C-T

Variant names:

• chr19-48758444-C-T
• rs11665841
• NM_019113.4:c.*224C>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.*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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019113.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF21	NM_019113.4	MANE Select	c.*224C>T		downstream_gene	N/A	NP_061986.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF21	ENST00000593756.6	TSL:1 MANE Select	c.*224C>T		downstream_gene	N/A	ENSP00000471477.1
	FGF21	ENST00000222157.5	TSL:1	c.*224C>T		downstream_gene	N/A	ENSP00000222157.3

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10855 AN: 150144 Hom.: 637 Cov.: 31

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

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: 44 AN: 1318

European-Non Finnish (NFE) AF: 0.0326 AC: 5457 AN: 167302

Other (OTH) AF: 0.0586 AC: 982 AN: 16764

GnomAD4 genome AF: 0.0724 AC: 10876 AN: 150248 Hom.: 640 Cov.: 31 AF XY: 0.0746 AC XY: 5469 AN XY: 73356

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: 88 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: 11 AN: 290

European-Non Finnish (NFE) AF: 0.0335 AC: 2266 AN: 67734

Other (OTH) AF: 0.0614 AC: 128 AN: 2084

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.82
PhyloP100		0.74

Splicing

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

Other links and lift over

dbSNP: rs11665841; hg19: chr19-49261701;