rs7567647

Positions:

• chr2-215432137-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_212482.4(FN1):​c.416-173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,078 control chromosomes in the GnomAD database, including 4,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.22 (4012 hom., cov: 32)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0880

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-215432137-G-A is Benign according to our data. Variant chr2-215432137-G-A is described in ClinVar as [Benign]. Clinvar id is 1268854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FN1	NM_212482.4	c.416-173C>T		intron_variant		ENST00000354785.11	NP_997647.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11	c.416-173C>T		intron_variant		1	NM_212482.4	ENSP00000346839.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33552 AN: 151960 Hom.: 4012 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.221 AC: 33567 AN: 152078 Hom.: 4012 Cov.: 32 AF XY: 0.216 AC XY: 16053 AN XY: 74356

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.202

Alfa AF: 0.222 Hom.: 678

Bravo AF: 0.215

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.53

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: rs7567647; hg19: chr2-216296860;