11-69698210-T-C

Variant names:

• chr11-69698210-T-C
• rs3737463
• NM_005117.3:c.*1052A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000294312.4(FGF19):​c.*1052A>G 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 ENST00000294312.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• Publications: 8 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000294312.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF19	NM_005117.3	MANE Select	c.*1052A>G		downstream_gene	N/A	NP_005108.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF19	ENST00000294312.4	TSL:1 MANE Select	c.*1052A>G		downstream_gene	N/A	ENSP00000294312.3

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

African (AFR) AF: 0.163 AC: 14 AN: 86

American (AMR) AF: 0.525 AC: 21 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 77 AN: 98

East Asian (EAS) AF: 0.208 AC: 118 AN: 566

South Asian (SAS) AF: 0.200 AC: 2 AN: 10

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 4 AN: 8

European-Non Finnish (NFE) AF: 0.765 AC: 768 AN: 1004

Other (OTH) AF: 0.614 AC: 102 AN: 166

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

African (AFR) AF: 0.250 AC: 10324 AN: 41272

American (AMR) AF: 0.719 AC: 10973 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2340 AN: 3462

East Asian (EAS) AF: 0.382 AC: 1939 AN: 5076

South Asian (SAS) AF: 0.589 AC: 2817 AN: 4786

European-Finnish (FIN) AF: 0.774 AC: 8143 AN: 10520

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52648 AN: 67942

Other (OTH) AF: 0.607 AC: 1282 AN: 2112

Alfa AF: 0.719 Hom.: 73061

Bravo AF: 0.583

Asia WGS AF: 0.503 AC: 1747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.64
DANN	Benign	0.39
PhyloP100		-0.91
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3737463; hg19: chr11-69512978;