rs1307968

Positions:

• chr11-69700655-G-A
• chr11-69700655-G-C
• chr11-69700655-G-T

Variant summary

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

The NM_005117.3(FGF19):​c.337-1079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,292 control chromosomes in the GnomAD database, including 59,070 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 0.88 (59070 hom., cov: 33)
• Consequence: FGF19 NM_005117.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF19	NM_005117.3	c.337-1079C>T		intron_variant		ENST00000294312.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF19	ENST00000294312.4	c.337-1079C>T		intron_variant		1	NM_005117.3	P1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133994 AN: 152174 Hom.: 59008 Cov.: 33

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.881

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.881 AC: 134117 AN: 152292 Hom.: 59070 Cov.: 33 AF XY: 0.882 AC XY: 65642 AN XY: 74462

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.883

Alfa AF: 0.874 Hom.: 62215

Bravo AF: 0.887

Asia WGS AF: 0.891 AC: 3099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.8
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1307968; hg19: chr11-69515423;