NM_005117.3:c.*692T>C

Variant names:

• chr11-69698570-A-G
• rs948992
• NM_005117.3:c.*692T>C

Variant summary

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

The NM_005117.3(FGF19):​c.*692T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 191,524 control chromosomes in the GnomAD database, including 11,762 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 0.34 (9275 hom., cov: 33)
  • Exomes 𝑓: 0.34 (2487 hom.)
• Consequence: FGF19 NM_005117.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82
• Publications: 18 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF19	NM_005117.3	MANE Select	c.*692T>C		3_prime_UTR	Exon 3 of 3	NP_005108.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF19	ENST00000294312.4	TSL:1 MANE Select	c.*692T>C		3_prime_UTR	Exon 3 of 3	ENSP00000294312.3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52038 AN: 151888 Hom.: 9273 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.342 AC: 13522 AN: 39518 Hom.: 2487 Cov.: 0 AF XY: 0.341 AC XY: 6269 AN XY: 18362

African (AFR) AF: 0.405 AC: 620 AN: 1532

American (AMR) AF: 0.282 AC: 270 AN: 956

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 793 AN: 2534

East Asian (EAS) AF: 0.508 AC: 3552 AN: 6986

South Asian (SAS) AF: 0.506 AC: 167 AN: 330

European-Finnish (FIN) AF: 0.404 AC: 21 AN: 52

Middle Eastern (MID) AF: 0.417 AC: 101 AN: 242

European-Non Finnish (NFE) AF: 0.294 AC: 6947 AN: 23660

Other (OTH) AF: 0.326 AC: 1051 AN: 3226

GnomAD4 genome AF: 0.342 AC: 52050 AN: 152006 Hom.: 9275 Cov.: 33 AF XY: 0.348 AC XY: 25893 AN XY: 74306

African (AFR) AF: 0.403 AC: 16721 AN: 41470

American (AMR) AF: 0.263 AC: 4020 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3470

East Asian (EAS) AF: 0.513 AC: 2627 AN: 5118

South Asian (SAS) AF: 0.477 AC: 2299 AN: 4824

European-Finnish (FIN) AF: 0.388 AC: 4098 AN: 10570

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20063 AN: 67956

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.315 Hom.: 16073

Bravo AF: 0.335

Asia WGS AF: 0.458 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.49
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs948992; hg19: chr11-69513338;