rs10932613

chr2-215369934-G-Achr2-215369934-G-Cchr2-215369934-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_212482.4(FN1):c.6853+360C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,158 control chromosomes in the GnomAD database, including 1,691 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 0.13 (1691 hom., cov: 32)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

Genes affected

FN1 (HGNC:3778): (fibronectin 1) This gene encodes fibronectin, a glycoprotein present in a soluble dimeric form in plasma, and in a dimeric or multimeric form at the cell surface and in extracellular matrix. The encoded preproprotein is proteolytically processed to generate the mature protein. Fibronectin is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. The gene has three regions subject to alternative splicing, with the potential to produce 20 different transcript variants, at least one of which encodes an isoform that undergoes proteolytic processing. The full-length nature of some variants has not been determined. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN1	NM_212482.4	c.6853+360C>T		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11	c.6853+360C>T		intron_variant		1	NM_212482.4	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20041 AN: 152040 Hom.: 1694 Cov.: 32

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.132 AC: 20028 AN: 152158 Hom.: 1691 Cov.: 32 AF XY: 0.135 AC XY: 10064 AN XY: 74380

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.147

Alfa AF: 0.145 Hom.: 369

Bravo AF: 0.129

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	9.6
Dann	Benign	0.89

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

Other links and lift over

dbSNP: rs10932613; hg19: chr2-216234657;