2-215361907-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_212482.4(FN1):c.7362+62C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00964 in 1,560,622 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (102 hom.)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.594

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]

ATIC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-215361907-G-C is Benign according to our data. Variant chr2-215361907-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1211335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1539/151546) while in subpopulation NFE AF= 0.0139 (943/67902). AF 95% confidence interval is 0.0132. There are 19 homozygotes in gnomad4. There are 832 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1539 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN1	NM_212482.4	c.7362+62C>G		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11	c.7362+62C>G		intron_variant		1	NM_212482.4	P1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1539 AN: 151416 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00223

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00434

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00446

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00722

GnomAD4 exome AF: 0.00958 AC: 13502 AN: 1409076 Hom.: 102 Cov.: 28 AF XY: 0.00954 AC XY: 6693 AN XY: 701582

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.000600

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00396

Gnomad4 FIN exome AF: 0.0312

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.00711

GnomAD4 genome AF: 0.0102 AC: 1539 AN: 151546 Hom.: 19 Cov.: 32 AF XY: 0.0112 AC XY: 832 AN XY: 74026

Gnomad4 AFR AF: 0.00223

Gnomad4 AMR AF: 0.00434

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00446

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.00714

Alfa AF: 0.0143 Hom.: 3

Bravo AF: 0.00640

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	FN1: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.9
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.38		Position offset: 5

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

Publications

LitVar

Other links and lift over

dbSNP: rs114497844; hg19: chr2-216226630;