Variant 2-215361645-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_212482.4(FN1):c.7363-20dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,576,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

FN1
NM_212482.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0510

Variant links:

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 links:

ATIC (HGNC:794): (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]

ATIC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-215361645-G-GA is Benign according to our data. Variant chr2-215361645-G-GA is described in ClinVar as [Benign]. Clinvar id is 3607130.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000423 (604/1427040) while in subpopulation NFE AF= 0.00051 (552/1082176). AF 95% confidence interval is 0.000475. There are 0 homozygotes in gnomad4_exome. There are 267 alleles in male gnomad4_exome subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 604 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FN1	NM_212482.4 link	c.7363-20dupT		intron_variant	Intron 45 of 45	ENST00000354785.11	NP_997647.2	P02751-15Q6MZM7Q9UQS6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11 link	c.7363-20_7363-19insT		intron_variant	Intron 45 of 45	1	NM_212482.4	ENSP00000346839.4		P02751-15

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

149746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000999

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000423

AC:

604

AN:

1427040

Hom.:

Cov.:

AF XY:

0.000375

AC XY:

267

AN XY:

711560

show subpopulations

Gnomad4 AFR exome

AF:

0.000245

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000510

Gnomad4 OTH exome

AF:

0.000372

GnomAD4 genome

AF:

0.0000200

AC:

AN:

149746

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

72978

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000664

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000999

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over