rs255693

Variant names:

• chr5-128298710-G-C
• rs255693
• NM_001999.4:c.6166+2107C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-128298710-G-C
• chr5-128298710-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001999.4(FBN2):​c.6166+2107C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,740 control chromosomes in the GnomAD database, including 24,005 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (24005 hom., cov: 31)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 2 publications found

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

FBN2 Gene-Disease associations (from GenCC):

• congenital contractural arachnodactyly

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• carpal tunnel syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• macular degeneration, early-onset

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.6166+2107C>G		intron_variant	Intron 48 of 64	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.6013+2107C>G		intron_variant	Intron 47 of 63		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.6166+2107C>G		intron_variant	Intron 48 of 64	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000703783.1	n.2950+2107C>G		intron_variant	Intron 23 of 37
FBN2	ENST00000703785.1	n.2869+2107C>G		intron_variant	Intron 22 of 26

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82583 AN: 151624 Hom.: 23993 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.544 AC: 82616 AN: 151740 Hom.: 24005 Cov.: 31 AF XY: 0.554 AC XY: 41084 AN XY: 74134

African (AFR) AF: 0.332 AC: 13751 AN: 41380

American (AMR) AF: 0.606 AC: 9241 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2178 AN: 3462

East Asian (EAS) AF: 0.803 AC: 4136 AN: 5152

South Asian (SAS) AF: 0.648 AC: 3106 AN: 4796

European-Finnish (FIN) AF: 0.712 AC: 7488 AN: 10522

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40867 AN: 67880

Other (OTH) AF: 0.548 AC: 1151 AN: 2102

Alfa AF: 0.569 Hom.: 3033

Bravo AF: 0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.84
PhyloP100		0.089
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

Other links and lift over

dbSNP: rs255693; hg19: chr5-127634402;