dbSNP rs1640233: FSCN1:p.Phe336Phe (chr7-5603514-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003088.4(FSCN1):c.1008T>C(p.Phe336Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,613,870 control chromosomes in the GnomAD database, including 30,378 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 0.22 ( 3840 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26538 hom. )

Consequence

FSCN1
NM_003088.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

FSCN1 (HGNC:11148): (fascin actin-bundling protein 1) This gene encodes a member of the fascin family of actin-binding proteins. Fascin proteins organize F-actin into parallel bundles, and are required for the formation of actin-based cellular protrusions. The encoded protein plays a critical role in cell migration, motility, adhesion and cellular interactions. Expression of this gene is known to be regulated by several microRNAs, and overexpression of this gene may play a role in the metastasis of multiple types of cancer by increasing cell motility. Expression of this gene is also a marker for Reed-Sternberg cells in Hodgkin's lymphoma. A pseudogene of this gene is located on the long arm of chromosome 15. [provided by RefSeq, Sep 2011]

FSCN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN1	NM_003088.4 link	c.1008T>C	p.Phe336Phe	synonymous_variant	Exon 3 of 5	ENST00000382361.8	NP_003079.1	Q16658A0A384MEG1B3KTA3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSCN1	ENST00000382361.8 link	c.1008T>C	p.Phe336Phe	synonymous_variant	Exon 3 of 5	1	NM_003088.4	ENSP00000371798.3		Q16658

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33302

AN:

151980

Hom.:

3838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.197

GnomAD3 exomes

AF:

0.197

AC:

49386

AN:

251176

Hom.:

5241

AF XY:

0.200

AC XY:

27169

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.302

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.280

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.187

AC:

272738

AN:

1461774

Hom.:

26538

Cov.:

AF XY:

0.189

AC XY:

137758

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.177

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.219

AC:

33343

AN:

152096

Hom.:

3840

Cov.:

AF XY:

0.218

AC XY:

16221

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.302

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.183

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.194

Hom.:

1610

Bravo

AF:

0.219

Asia WGS

AF:

0.253

AC:

879

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.8

DANN

Benign

0.51

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