rs31777

Variant names:

• chr5-177096561-C-A
• rs31777
• NM_213647.3:c.2016-43C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-177096561-C-A
• chr5-177096561-C-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.2016-43C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,606,570 control chromosomes in the GnomAD database, including 519,089 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 (47922 hom., cov: 32)
  • Exomes 𝑓: 0.80 (471167 hom.)
• Consequence: FGFR4 NM_213647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 18 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=-0.81).
• 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.2016-43C>A		intron_variant	Intron 15 of 17	ENST00000292408.9	NP_998812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR4	ENST00000292408.9	c.2016-43C>A		intron_variant	Intron 15 of 17	1	NM_213647.3	ENSP00000292408.4
FGFR4	ENST00000502906.5	c.2016-43C>A		intron_variant	Intron 15 of 17	1		ENSP00000424960.1
FGFR4	ENST00000393637.5	c.1896-43C>A		intron_variant	Intron 13 of 15	1		ENSP00000377254.1
FGFR4	ENST00000393648.6	c.1812-43C>A		intron_variant	Intron 15 of 17	2		ENSP00000377259.2

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120270 AN: 151924 Hom.: 47863 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.778

GnomAD2 exomes AF: 0.831 AC: 204066 AN: 245480 AF XY: 0.832

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.879

Gnomad ASJ exome AF: 0.782

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.780

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.803 AC: 1167801 AN: 1454528 Hom.: 471167 Cov.: 39 AF XY: 0.805 AC XY: 582330 AN XY: 723344

African (AFR) AF: 0.753 AC: 25109 AN: 33366

American (AMR) AF: 0.872 AC: 38381 AN: 44006

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 19985 AN: 25584

East Asian (EAS) AF: 1.00 AC: 39658 AN: 39676

South Asian (SAS) AF: 0.916 AC: 78278 AN: 85494

European-Finnish (FIN) AF: 0.843 AC: 44725 AN: 53046

Middle Eastern (MID) AF: 0.743 AC: 4258 AN: 5734

European-Non Finnish (NFE) AF: 0.785 AC: 868887 AN: 1107562

Other (OTH) AF: 0.808 AC: 48520 AN: 60060

GnomAD4 genome AF: 0.792 AC: 120388 AN: 152042 Hom.: 47922 Cov.: 32 AF XY: 0.797 AC XY: 59236 AN XY: 74314

African (AFR) AF: 0.751 AC: 31111 AN: 41446

American (AMR) AF: 0.811 AC: 12400 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2741 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5135 AN: 5140

South Asian (SAS) AF: 0.928 AC: 4473 AN: 4818

European-Finnish (FIN) AF: 0.849 AC: 9013 AN: 10618

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 52981 AN: 67948

Other (OTH) AF: 0.781 AC: 1650 AN: 2112

Alfa AF: 0.784 Hom.: 8592

Bravo AF: 0.784

Asia WGS AF: 0.950 AC: 3306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		-0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs31777; hg19: chr5-176523562; COSMIC: COSV99448718;