dbSNP rs434434: FGFR4:c.91+259A>G (chr5-177089952-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_213647.3(FGFR4):c.91+259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 688,110 control chromosomes in the GnomAD database, including 228,865 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 0.79 ( 47992 hom., cov: 31)

Exomes 𝑓: 0.82 ( 180873 hom. )

Consequence

FGFR4
NM_213647.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Variant links:

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]

FGFR4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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 link	c.91+259A>G		intron_variant	Intron 2 of 17	ENST00000292408.9	NP_998812.1	P22455-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR4	ENST00000292408.9 link	c.91+259A>G		intron_variant	Intron 2 of 17	1	NM_213647.3	ENSP00000292408.4		P22455-1

Frequencies

GnomAD3 genomes

AF:

0.792

AC:

120394

AN:

151968

Hom.:

47933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.812

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.929

Gnomad FIN

AF:

0.849

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.780

Gnomad OTH

AF:

0.778

GnomAD3 exomes

AF:

0.841

AC:

109362

AN:

129990

Hom.:

46382

AF XY:

0.844

AC XY:

59798

AN XY:

70838

show subpopulations

Gnomad AFR exome

AF:

0.739

Gnomad AMR exome

AF:

0.873

Gnomad ASJ exome

AF:

0.784

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.920

Gnomad FIN exome

AF:

0.841

Gnomad NFE exome

AF:

0.780

Gnomad OTH exome

AF:

0.806

GnomAD4 exome

AF:

0.818

AC:

438676

AN:

536024

Hom.:

180873

Cov.:

AF XY:

0.823

AC XY:

238780

AN XY:

290302

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.867

Gnomad4 ASJ exome

AF:

0.782

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.915

Gnomad4 FIN exome

AF:

0.843

Gnomad4 NFE exome

AF:

0.781

Gnomad4 OTH exome

AF:

0.805

GnomAD4 genome

AF:

0.792

AC:

120512

AN:

152086

Hom.:

47992

Cov.:

AF XY:

0.798

AC XY:

59321

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.751

Gnomad4 AMR

AF:

0.812

Gnomad4 ASJ

AF:

0.790

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.929

Gnomad4 FIN

AF:

0.849

Gnomad4 NFE

AF:

0.780

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.783

Hom.:

9528

Bravo

AF:

0.785

Asia WGS

AF:

0.951

AC:

3308

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.56

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over