rs114497844

Variant names:

• chr2-215361907-G-C
• rs114497844
• NM_212482.4:c.7362+62C>G

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.594
• Publications: 1 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]

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 Gene-Disease associations (from GenCC):

• AICA-ribosiduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1539 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FN1	NM_212482.4	c.7362+62C>G		intron_variant	Intron 45 of 45	ENST00000354785.11	NP_997647.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11	c.7362+62C>G		intron_variant	Intron 45 of 45	1	NM_212482.4	ENSP00000346839.4

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

African (AFR) AF: 0.00146 AC: 47 AN: 32214

American (AMR) AF: 0.00291 AC: 125 AN: 42970

Ashkenazi Jewish (ASJ) AF: 0.000600 AC: 15 AN: 24986

East Asian (EAS) AF: 0.00 AC: 0 AN: 37092

South Asian (SAS) AF: 0.00396 AC: 330 AN: 83420

European-Finnish (FIN) AF: 0.0312 AC: 1609 AN: 51612

Middle Eastern (MID) AF: 0.00105 AC: 5 AN: 4776

European-Non Finnish (NFE) AF: 0.0102 AC: 10959 AN: 1074046

Other (OTH) AF: 0.00711 AC: 412 AN: 57960

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

African (AFR) AF: 0.00223 AC: 92 AN: 41346

American (AMR) AF: 0.00434 AC: 66 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5072

South Asian (SAS) AF: 0.00446 AC: 21 AN: 4710

European-Finnish (FIN) AF: 0.0369 AC: 388 AN: 10522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 943 AN: 67902

Other (OTH) AF: 0.00714 AC: 15 AN: 2100

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FN1: BS1, BS2 -

Dec 29, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.75
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114497844; hg19: chr2-216226630;