2-215361645-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_212482.4(FN1):c.7363-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,579,014 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.650

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-215361645-G-A is Benign according to our data. Variant chr2-215361645-G-A is described in ClinVar as [Benign]. Clinvar id is 1589584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00168 (252/149854) while in subpopulation AFR AF= 0.006 (245/40810). AF 95% confidence interval is 0.00539. There are 1 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 252 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN1	NM_212482.4	c.7363-19C>T		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11	c.7363-19C>T		intron_variant		1	NM_212482.4	P1

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 252 AN: 149744 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000970

GnomAD3 exomes AF: 0.000391 AC: 95 AN: 242898 Hom.: 1 AF XY: 0.000349 AC XY: 46 AN XY: 131662

Gnomad AFR exome AF: 0.00554

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad SAS exome AF: 0.0000676

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000909

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.000155 AC: 221 AN: 1429160 Hom.: 1 Cov.: 26 AF XY: 0.000142 AC XY: 101 AN XY: 712562

Gnomad4 AFR exome AF: 0.00546

Gnomad4 AMR exome AF: 0.000181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000352

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000369

Gnomad4 OTH exome AF: 0.000422

GnomAD4 genome AF: 0.00168 AC: 252 AN: 149854 Hom.: 1 Cov.: 32 AF XY: 0.00187 AC XY: 137 AN XY: 73096

Gnomad4 AFR AF: 0.00600

Gnomad4 AMR AF: 0.000265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.000961

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.00188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 28, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.1
Dann	Benign	0.29

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: rs201573768; hg19: chr2-216226368;