rs446382

Variant names:

• chr5-177090460-T-G
• rs446382
• NM_213647.3:c.162T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-177090460-T-G
• chr5-177090460-T-A
• chr5-177090460-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_213647.3(FGFR4):​c.162T>G​(p.Arg54Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,602,806 control chromosomes in the GnomAD database, including 443,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.71 (39083 hom., cov: 32)
  • Exomes 𝑓: 0.74 (403963 hom.)
• Consequence: FGFR4 NM_213647.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.479
• Publications: 25 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-177090460-T-G is Benign according to our data. Variant chr5-177090460-T-G is described in ClinVar as Benign. ClinVar VariationId is 3061016.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.479 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213647.3. 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
	FGFR4	NM_213647.3	MANE Select	c.162T>G	p.Arg54Arg	synonymous	Exon 3 of 18	NP_998812.1	P22455-1
	FGFR4	NM_001354984.2		c.162T>G	p.Arg54Arg	synonymous	Exon 3 of 18	NP_001341913.1	P22455-1
	FGFR4	NM_002011.5		c.162T>G	p.Arg54Arg	synonymous	Exon 3 of 18	NP_002002.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR4	ENST00000292408.9	TSL:1 MANE Select	c.162T>G	p.Arg54Arg	synonymous	Exon 3 of 18	ENSP00000292408.4	P22455-1
	FGFR4	ENST00000502906.5	TSL:1	c.162T>G	p.Arg54Arg	synonymous	Exon 3 of 18	ENSP00000424960.1	P22455-1
	FGFR4	ENST00000393637.5	TSL:1	c.162T>G	p.Arg54Arg	synonymous	Exon 2 of 16	ENSP00000377254.1	P22455-2

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108139 AN: 151942 Hom.: 39047 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.703

GnomAD2 exomes AF: 0.772 AC: 186567 AN: 241800 AF XY: 0.774

Gnomad AFR exome AF: 0.604

Gnomad AMR exome AF: 0.844

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.972

Gnomad FIN exome AF: 0.756

Gnomad NFE exome AF: 0.717

Gnomad OTH exome AF: 0.737

GnomAD4 exome AF: 0.743 AC: 1078055 AN: 1450746 Hom.: 403963 Cov.: 77 AF XY: 0.747 AC XY: 538620 AN XY: 721374

African (AFR) AF: 0.609 AC: 20329 AN: 33408

American (AMR) AF: 0.834 AC: 37009 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 18275 AN: 25550

East Asian (EAS) AF: 0.978 AC: 38768 AN: 39630

South Asian (SAS) AF: 0.888 AC: 75858 AN: 85400

European-Finnish (FIN) AF: 0.755 AC: 36509 AN: 48336

Middle Eastern (MID) AF: 0.662 AC: 3778 AN: 5704

European-Non Finnish (NFE) AF: 0.724 AC: 802875 AN: 1108260

Other (OTH) AF: 0.743 AC: 44654 AN: 60086

GnomAD4 genome AF: 0.712 AC: 108224 AN: 152060 Hom.: 39083 Cov.: 32 AF XY: 0.718 AC XY: 53389 AN XY: 74324

African (AFR) AF: 0.612 AC: 25369 AN: 41448

American (AMR) AF: 0.754 AC: 11537 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2518 AN: 3468

East Asian (EAS) AF: 0.976 AC: 5044 AN: 5170

South Asian (SAS) AF: 0.900 AC: 4342 AN: 4822

European-Finnish (FIN) AF: 0.761 AC: 8051 AN: 10582

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49065 AN: 67966

Other (OTH) AF: 0.702 AC: 1479 AN: 2108

Alfa AF: 0.712 Hom.: 10754

Bravo AF: 0.704

Asia WGS AF: 0.883 AC: 3073 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FGFR4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.7
DANN	Benign	0.48
PhyloP100		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs446382; hg19: chr5-176517461; COSMIC: COSV52802425; COSMIC: COSV52802425;