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

Variant summary

Our verdict is Benign. The variant received -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

Publications

21 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.197

AC:

49386

AN:

251176

AF XY:

0.200

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 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

African (AFR)

AF:

0.308

AC:

10315

AN:

33478

American (AMR)

AF:

0.152

AC:

6800

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

5709

AN:

26132

East Asian (EAS)

AF:

0.162

AC:

6437

AN:

39700

South Asian (SAS)

AF:

0.276

AC:

23812

AN:

86258

European-Finnish (FIN)

AF:

0.186

AC:

9929

AN:

53370

Middle Eastern (MID)

AF:

0.203

AC:

1171

AN:

5768

European-Non Finnish (NFE)

AF:

0.177

AC:

197019

AN:

1111956

Other (OTH)

AF:

0.191

AC:

11546

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

13892

27784

41675

55567

69459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7044

14088

21132

28176

35220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.219

AC:

33343

AN:

152096

Hom.:

3840

Cov.:

AF XY:

0.218

AC XY:

16221

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.302

AC:

12548

AN:

41484

American (AMR)

AF:

0.186

AC:

2842

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

758

AN:

3470

East Asian (EAS)

AF:

0.152

AC:

786

AN:

5164

South Asian (SAS)

AF:

0.270

AC:

1301

AN:

4820

European-Finnish (FIN)

AF:

0.187

AC:

1981

AN:

10592

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12446

AN:

67974

Other (OTH)

AF:

0.200

AC:

421

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1358

2717

4075

5434

6792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

2128

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

(source)

DANN

Benign

0.51

PhyloP100

-1.6

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over