rs10932613

Variant names:

• chr2-215369934-G-A
• rs10932613
• NM_212482.4:c.6853+360C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-215369934-G-A
• chr2-215369934-G-C
• chr2-215369934-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

FN1 Gene-Disease associations (from GenCC):

• spondylometaphyseal dysplasia, 'corner fracture' type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• glomerulopathy with fibronectin deposits 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• fibronectin glomerulopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212482.4. 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
	FN1	NM_212482.4	MANE Select	c.6853+360C>T		intron	N/A	NP_997647.2	P02751-15
	FN1	NM_001306129.2		c.6760+360C>T		intron	N/A	NP_001293058.2	P02751-7
	FN1	NM_001365517.2		c.6583+360C>T		intron	N/A	NP_001352446.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN1	ENST00000354785.11	TSL:1 MANE Select	c.6853+360C>T		intron	N/A	ENSP00000346839.4	P02751-15
	FN1	ENST00000323926.10	TSL:1	c.6760+360C>T		intron	N/A	ENSP00000323534.6	P02751-7
	FN1	ENST00000336916.8	TSL:1	c.6487+360C>T		intron	N/A	ENSP00000338200.4	P02751-3

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

African (AFR) AF: 0.0334 AC: 1387 AN: 41542

American (AMR) AF: 0.184 AC: 2812 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5162

South Asian (SAS) AF: 0.210 AC: 1014 AN: 4824

European-Finnish (FIN) AF: 0.157 AC: 1657 AN: 10568

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10933 AN: 68006

Other (OTH) AF: 0.147 AC: 310 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.6
DANN	Benign	0.89
PhyloP100		-0.095
Mutation Taster		=100/0	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: rs10932613; hg19: chr2-216234657;