rs10478813

Variant names:

• chr5-128495572-G-C
• rs10478813
• NM_001999.4:c.628+23701C>G

Variant summary

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

The NM_001999.4(FBN2):​c.628+23701C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 151,970 control chromosomes in the GnomAD database, including 705 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 0.087 (705 hom., cov: 32)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 1 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• carpal tunnel syndrome

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

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001999.4. 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
	FBN2	NM_001999.4	MANE Select	c.628+23701C>G		intron	N/A	NP_001990.2	P35556-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN2	ENST00000262464.9	TSL:1 MANE Select	c.628+23701C>G		intron	N/A	ENSP00000262464.4	P35556-1
	FBN2	ENST00000502468.5	TSL:1	c.628+23701C>G		intron	N/A	ENSP00000424753.1	E9PHW4
	FBN2	ENST00000939405.1		c.529+23701C>G		intron	N/A	ENSP00000609464.1

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13237 AN: 151854 Hom.: 700 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.0889

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

GnomAD4 genome AF: 0.0873 AC: 13274 AN: 151970 Hom.: 705 Cov.: 32 AF XY: 0.0891 AC XY: 6620 AN XY: 74266

African (AFR) AF: 0.133 AC: 5518 AN: 41464

American (AMR) AF: 0.0827 AC: 1263 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 185 AN: 3466

East Asian (EAS) AF: 0.107 AC: 553 AN: 5166

South Asian (SAS) AF: 0.163 AC: 784 AN: 4812

European-Finnish (FIN) AF: 0.0757 AC: 799 AN: 10552

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0578 AC: 3924 AN: 67912

Other (OTH) AF: 0.0918 AC: 194 AN: 2114

Alfa AF: 0.0697 Hom.: 60

Bravo AF: 0.0876

Asia WGS AF: 0.166 AC: 573 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.28
DANN	Benign	0.32
PhyloP100		-2.3
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: rs10478813; hg19: chr5-127831265;