rs1640233

Variant names:

• chr7-5603514-T-C
• rs1640233
• NM_003088.4:c.1008T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 21 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003088.4. 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
	FSCN1	NM_003088.4	MANE Select	c.1008T>C	p.Phe336Phe	synonymous	Exon 3 of 5	NP_003079.1	Q16658

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCN1	ENST00000382361.8	TSL:1 MANE Select	c.1008T>C	p.Phe336Phe	synonymous	Exon 3 of 5	ENSP00000371798.3	Q16658
	FSCN1	ENST00000905052.1		c.1008T>C	p.Phe336Phe	synonymous	Exon 3 of 5	ENSP00000575111.1
	FSCN1	ENST00000905053.1		c.999T>C	p.Phe333Phe	synonymous	Exon 3 of 5	ENSP00000575112.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33302 AN: 151980 Hom.: 3838 Cov.: 32

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

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.: 34 AF XY: 0.189 AC XY: 137758 AN XY: 727184

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

GnomAD4 genome AF: 0.219 AC: 33343 AN: 152096 Hom.: 3840 Cov.: 32 AF XY: 0.218 AC XY: 16221 AN XY: 74354

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: 40 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12446 AN: 67974

Other (OTH) AF: 0.200 AC: 421 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.8
DANN	Benign	0.51
PhyloP100		-1.6
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1640233; hg19: chr7-5643145; COSMIC: COSV61017542;