rs6707530

Variant names:

• chr2-215375861-T-G
• rs6707530
• NM_212482.4:c.5888-143A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-215375861-T-G
• chr2-215375861-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_212482.4(FN1):​c.5888-143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 693,018 control chromosomes in the GnomAD database, including 38,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8480 hom., cov: 33)
  • Exomes 𝑓: 0.30 (29590 hom.)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.928
• Publications: 11 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]

FN1 Gene-Disease associations (from GenCC):

• spondylometaphyseal dysplasia, 'corner fracture' type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• glomerulopathy with fibronectin deposits 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• fibronectin glomerulopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-215375861-T-G is Benign according to our data. Variant chr2-215375861-T-G is described in ClinVar as Benign. ClinVar VariationId is 1248775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212482.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN1	NM_212482.4	MANE Select	c.5888-143A>C		intron	N/A	NP_997647.2	P02751-15
	FN1	NM_001306129.2		c.5888-143A>C		intron	N/A	NP_001293058.2	P02751-7
	FN1	NM_001365517.2		c.5618-143A>C		intron	N/A	NP_001352446.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN1	ENST00000354785.11	TSL:1 MANE Select	c.5888-143A>C		intron	N/A	ENSP00000346839.4	P02751-15
	FN1	ENST00000323926.10	TSL:1	c.5888-143A>C		intron	N/A	ENSP00000323534.6	P02751-7
	FN1	ENST00000336916.8	TSL:1	c.5615-143A>C		intron	N/A	ENSP00000338200.4	P02751-3

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47714 AN: 151972 Hom.: 8473 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.298 AC: 160994 AN: 540928 Hom.: 29590 AF XY: 0.292 AC XY: 85440 AN XY: 292814

African (AFR) AF: 0.371 AC: 5640 AN: 15204

American (AMR) AF: 0.440 AC: 14829 AN: 33714

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 6870 AN: 18976

East Asian (EAS) AF: 0.817 AC: 25446 AN: 31142

South Asian (SAS) AF: 0.250 AC: 15243 AN: 60892

European-Finnish (FIN) AF: 0.233 AC: 9792 AN: 41954

Middle Eastern (MID) AF: 0.324 AC: 1098 AN: 3394

European-Non Finnish (NFE) AF: 0.238 AC: 72994 AN: 306318

Other (OTH) AF: 0.310 AC: 9082 AN: 29334

GnomAD4 genome AF: 0.314 AC: 47758 AN: 152090 Hom.: 8480 Cov.: 33 AF XY: 0.319 AC XY: 23748 AN XY: 74350

African (AFR) AF: 0.370 AC: 15362 AN: 41478

American (AMR) AF: 0.395 AC: 6035 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4097 AN: 5170

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4816

European-Finnish (FIN) AF: 0.247 AC: 2610 AN: 10572

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16071 AN: 67992

Other (OTH) AF: 0.322 AC: 680 AN: 2114

Alfa AF: 0.262 Hom.: 9230

Bravo AF: 0.332

Asia WGS AF: 0.508 AC: 1769 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.80
PhyloP100		-0.93
PromoterAI		0.0044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6707530;

hg19: chr2-216240584;