7-127593014-C-T

Variant names:

• chr7-127593014-C-T
• rs3757791
• ENST00000478328.1:n.543+1063C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000478328.1(FSCN3):​n.543+1063C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 152,252 control chromosomes in the GnomAD database, including 890 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 0.083 (890 hom., cov: 32)
• Consequence: FSCN3 ENST00000478328.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 4 publications found

Genes affected

FSCN3 (HGNC:3961): (fascin actin-bundling protein 3) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament bundle assembly; cell migration; and establishment or maintenance of cell polarity. Predicted to be located in cytoskeleton. Predicted to be active in several cellular components, including lamellipodium; microvillus; and ruffle. [provided by Alliance of Genome Resources, Apr 2022]

GCC1 (HGNC:19095): (GRIP and coiled-coil domain containing 1) The protein encoded by this gene is a peripheral membrane protein. It is sensitive to brefeldin A. This encoded protein contains a GRIP domain which is thought to be used in targeting. It may play a role in the organization of trans-Golgi network subcompartment involved with membrane transport. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSCN3	ENST00000478328.1	n.543+1063C>T		intron_variant	Intron 1 of 1	1
GCC1	ENST00000473728.1	n.114+484G>A		intron_variant	Intron 1 of 3	3
GCC1	ENST00000497650.1	n.109+484G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12544 AN: 152134 Hom.: 885 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0621

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0683

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0825 AC: 12566 AN: 152252 Hom.: 890 Cov.: 32 AF XY: 0.0833 AC XY: 6203 AN XY: 74448

African (AFR) AF: 0.187 AC: 7766 AN: 41522

American (AMR) AF: 0.0572 AC: 875 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 71 AN: 3472

East Asian (EAS) AF: 0.0834 AC: 431 AN: 5168

South Asian (SAS) AF: 0.104 AC: 502 AN: 4834

European-Finnish (FIN) AF: 0.0621 AC: 659 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0307 AC: 2089 AN: 68016

Other (OTH) AF: 0.0671 AC: 142 AN: 2116

Alfa AF: 0.0439 Hom.: 1242

Bravo AF: 0.0856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.4
DANN	Benign	0.42
PhyloP100		-0.073

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3757791; hg19: chr7-127233068;