19-48758426-G-T

Variant names:

• chr19-48758426-G-T
• rs11665896
• NM_019113.4:c.*206G>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.*206G>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 454,270 control chromosomes in the GnomAD database, including 5,483 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 0.13 (2630 hom., cov: 31)
  • Exomes 𝑓: 0.079 (2853 hom.)
• Consequence: FGF21 NM_019113.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF21	NM_019113.4	c.*206G>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.*206G>T		downstream_gene_variant		1	NM_019113.4	ENSP00000471477.1
FGF21	ENST00000222157.5	c.*206G>T		downstream_gene_variant		1		ENSP00000222157.3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19998 AN: 151558 Hom.: 2609 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0272

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0993

GnomAD4 exome AF: 0.0785 AC: 23760 AN: 302602 Hom.: 2853 AF XY: 0.0763 AC XY: 11879 AN XY: 155634

African (AFR) AF: 0.327 AC: 2472 AN: 7562

American (AMR) AF: 0.119 AC: 1177 AN: 9856

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 224 AN: 10078

East Asian (EAS) AF: 0.407 AC: 9363 AN: 23022

South Asian (SAS) AF: 0.121 AC: 1606 AN: 13256

European-Finnish (FIN) AF: 0.0245 AC: 574 AN: 23400

Middle Eastern (MID) AF: 0.0422 AC: 61 AN: 1446

European-Non Finnish (NFE) AF: 0.0349 AC: 6815 AN: 195342

Other (OTH) AF: 0.0788 AC: 1468 AN: 18640

GnomAD4 genome AF: 0.132 AC: 20058 AN: 151668 Hom.: 2630 Cov.: 31 AF XY: 0.133 AC XY: 9850 AN XY: 74126

African (AFR) AF: 0.324 AC: 13390 AN: 41290

American (AMR) AF: 0.111 AC: 1697 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 94 AN: 3462

East Asian (EAS) AF: 0.274 AC: 1402 AN: 5118

South Asian (SAS) AF: 0.117 AC: 560 AN: 4796

European-Finnish (FIN) AF: 0.0277 AC: 290 AN: 10486

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0343 AC: 2332 AN: 67952

Other (OTH) AF: 0.0992 AC: 209 AN: 2106

Alfa AF: 0.0171 Hom.: 10

Bravo AF: 0.149

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.54
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs11665896; hg19: chr19-49261683;