rs55701137

Variant names:

• chr5-177090800-G-A
• rs55701137
• NM_213647.3:c.411G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-177090800-G-A
• chr5-177090800-G-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_213647.3(FGFR4):​c.411G>A​(p.Ser137Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,614,022 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (49 hom.)
• Consequence: FGFR4 NM_213647.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.008).
• BP6: Variant 5-177090800-G-A is Benign according to our data. Variant chr5-177090800-G-A is described in ClinVar as Benign. ClinVar VariationId is 773176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.78 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 49 gene

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.411G>A	p.Ser137Ser	synonymous	Exon 4 of 18	NP_998812.1	P22455-1
	FGFR4	NM_001354984.2		c.411G>A	p.Ser137Ser	synonymous	Exon 4 of 18	NP_001341913.1	P22455-1
	FGFR4	NM_002011.5		c.411G>A	p.Ser137Ser	synonymous	Exon 4 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.411G>A	p.Ser137Ser	synonymous	Exon 4 of 18	ENSP00000292408.4	P22455-1
	FGFR4	ENST00000502906.5	TSL:1	c.411G>A	p.Ser137Ser	synonymous	Exon 4 of 18	ENSP00000424960.1	P22455-1
	FGFR4	ENST00000393637.5	TSL:1	c.411G>A	p.Ser137Ser	synonymous	Exon 3 of 16	ENSP00000377254.1	P22455-2

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 645 AN: 152144 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00740

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00416 AC: 1046 AN: 251274 AF XY: 0.00409

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00365

Gnomad NFE exome AF: 0.00695

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00700 AC: 10228 AN: 1461760 Hom.: 49 Cov.: 34 AF XY: 0.00679 AC XY: 4935 AN XY: 727182

African (AFR) AF: 0.000956 AC: 32 AN: 33480

American (AMR) AF: 0.00141 AC: 63 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 59 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00177 AC: 153 AN: 86246

European-Finnish (FIN) AF: 0.00358 AC: 191 AN: 53412

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5766

European-Non Finnish (NFE) AF: 0.00840 AC: 9345 AN: 1111928

Other (OTH) AF: 0.00611 AC: 369 AN: 60390

GnomAD4 genome AF: 0.00424 AC: 645 AN: 152262 Hom.: 1 Cov.: 33 AF XY: 0.00410 AC XY: 305 AN XY: 74456

African (AFR) AF: 0.00149 AC: 62 AN: 41558

American (AMR) AF: 0.00177 AC: 27 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00740 AC: 503 AN: 67998

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00658 Hom.: 1

Bravo AF: 0.00409

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00747

EpiControl AF: 0.00622

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.15
DANN	Benign	0.45
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs55701137; hg19: chr5-176517801; COSMIC: COSV52809816; COSMIC: COSV52809816;