rs387598

Variant names:

• chr5-177090169-G-A
• rs387598
• NM_213647.3:c.92-221G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-177090169-G-A
• chr5-177090169-G-C
• chr5-177090169-G-T

Variant summary

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

The NM_213647.3(FGFR4):​c.92-221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 703,502 control chromosomes in the GnomAD database, including 215,179 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 0.75 (42709 hom., cov: 30)
  • Exomes 𝑓: 0.79 (172470 hom.)
• Consequence: FGFR4 NM_213647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 11 publications found

Genes affected

FGFR4 (HGNC:3691): (fibroblast growth factor receptor 4) The protein encoded by this gene is a tyrosine kinase and cell surface receptor for fibroblast growth factors. The encoded protein is involved in the regulation of several pathways, including cell proliferation, cell differentiation, cell migration, lipid metabolism, bile acid biosynthesis, vitamin D metabolism, glucose uptake, and phosphate homeostasis. This protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment, and a cytoplasmic tyrosine kinase domain. The extracellular portion interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR4	NM_213647.3	c.92-221G>A		intron_variant	Intron 2 of 17	ENST00000292408.9	NP_998812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR4	ENST00000292408.9	c.92-221G>A		intron_variant	Intron 2 of 17	1	NM_213647.3	ENSP00000292408.4

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113111 AN: 151594 Hom.: 42650 Cov.: 30

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.743

GnomAD2 exomes AF: 0.809 AC: 110024 AN: 135916 AF XY: 0.813

Gnomad AFR exome AF: 0.648

Gnomad AMR exome AF: 0.856

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.808

Gnomad NFE exome AF: 0.751

Gnomad OTH exome AF: 0.779

GnomAD4 exome AF: 0.787 AC: 434183 AN: 551790 Hom.: 172470 Cov.: 5 AF XY: 0.790 AC XY: 235848 AN XY: 298432

African (AFR) AF: 0.665 AC: 10539 AN: 15860

American (AMR) AF: 0.850 AC: 29275 AN: 34448

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 15050 AN: 19894

East Asian (EAS) AF: 0.999 AC: 31685 AN: 31706

South Asian (SAS) AF: 0.878 AC: 54497 AN: 62094

European-Finnish (FIN) AF: 0.810 AC: 26756 AN: 33028

Middle Eastern (MID) AF: 0.688 AC: 2773 AN: 4030

European-Non Finnish (NFE) AF: 0.750 AC: 240125 AN: 320268

Other (OTH) AF: 0.771 AC: 23483 AN: 30462

GnomAD4 genome AF: 0.746 AC: 113231 AN: 151712 Hom.: 42709 Cov.: 30 AF XY: 0.753 AC XY: 55809 AN XY: 74128

African (AFR) AF: 0.661 AC: 27275 AN: 41278

American (AMR) AF: 0.788 AC: 12037 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2659 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5164 AN: 5172

South Asian (SAS) AF: 0.893 AC: 4302 AN: 4818

European-Finnish (FIN) AF: 0.817 AC: 8578 AN: 10494

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.748 AC: 50804 AN: 67910

Other (OTH) AF: 0.746 AC: 1572 AN: 2106

Alfa AF: 0.752 Hom.: 17292

Bravo AF: 0.739

Asia WGS AF: 0.926 AC: 3222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.57
PhyloP100		-0.073
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
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: rs387598; hg19: chr5-176517170; COSMIC: COSV99448687;