rs3737463

chr11-69698210-T-Cchr11-69698210-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 11-69698210-T-C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 153,624 control chromosomes in the GnomAD database, including 31,866 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 0.60 (31464 hom., cov: 31)
  • Exomes 𝑓: 0.56 (402 hom.)
• Consequence: FGF19 NM_005117.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF19	NM_005117.3			downstream_gene_variant		ENST00000294312.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF19	ENST00000294312.4			downstream_gene_variant		1	NM_005117.3	P1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91384 AN: 151524 Hom.: 31458 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.604

GnomAD4 exome AF: 0.560 AC: 1108 AN: 1980 Hom.: 402 Cov.: 0 AF XY: 0.590 AC XY: 550 AN XY: 932

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.786

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 0.614

GnomAD4 genome AF: 0.603 AC: 91410 AN: 151644 Hom.: 31464 Cov.: 31 AF XY: 0.604 AC XY: 44721 AN XY: 74092

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.607

Alfa AF: 0.738 Hom.: 55176

Bravo AF: 0.583

Asia WGS AF: 0.503 AC: 1747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.64
Dann	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3737463; hg19: chr11-69512978;