rs770504584

Variant names:

• chr11-69699300-C-G
• rs770504584
• NM_005117.3:c.613G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-69699300-C-G
• chr11-69699300-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005117.3(FGF19):​c.613G>C​(p.Gly205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FGF19 NM_005117.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0100
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06613305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005117.3. 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
	FGF19	NM_005117.3	MANE Select	c.613G>C	p.Gly205Arg	missense	Exon 3 of 3	NP_005108.1	O95750

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF19	ENST00000294312.4	TSL:1 MANE Select	c.613G>C	p.Gly205Arg	missense	Exon 3 of 3	ENSP00000294312.3	O95750
	FGF19	ENST00000911903.1		c.613G>C	p.Gly205Arg	missense	Exon 4 of 4	ENSP00000581962.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.6
DANN	Benign	0.60
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.010
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.10
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.27		Loss of loop (P = 0.0512)
MVP		0.60
MPC		0.63
ClinPred		0.076	T
GERP RS		-0.69
Varity_R		0.036
gMVP		0.17
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs770504584; hg19: chr11-69514068;