rs27713

Variant names:

• chr5-128305091-G-A
• rs27713
• NM_001999.4:c.5675-9C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-128305091-G-A
• chr5-128305091-G-C
• chr5-128305091-G-T

Variant summary

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

The NM_001999.4(FBN2):​c.5675-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,572,472 control chromosomes in the GnomAD database, including 381,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (34471 hom., cov: 31)
  • Exomes 𝑓: 0.70 (347509 hom.)
• Consequence: FBN2 NM_001999.4 intron
• Scores: Splicing: ADA: 0.00001468
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: 0.918
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-128305091-G-A is Benign according to our data. Variant chr5-128305091-G-A is described in ClinVar as Benign. ClinVar VariationId is 129043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 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.5675-9C>T		intron	N/A	NP_001990.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN2	ENST00000262464.9	TSL:1 MANE Select	c.5675-9C>T		intron	N/A	ENSP00000262464.4
	FBN2	ENST00000939405.1		c.5576-9C>T		intron	N/A	ENSP00000609464.1
	FBN2	ENST00000939404.1		c.5522-9C>T		intron	N/A	ENSP00000609463.1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 101358 AN: 146238 Hom.: 34438 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.671

GnomAD2 exomes AF: 0.708 AC: 166381 AN: 235054 AF XY: 0.713

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.675

Gnomad ASJ exome AF: 0.708

Gnomad EAS exome AF: 0.858

Gnomad FIN exome AF: 0.767

Gnomad NFE exome AF: 0.698

Gnomad OTH exome AF: 0.713

GnomAD4 exome AF: 0.698 AC: 995491 AN: 1426126 Hom.: 347509 Cov.: 29 AF XY: 0.701 AC XY: 497590 AN XY: 710328

African (AFR) AF: 0.611 AC: 17606 AN: 28802

American (AMR) AF: 0.683 AC: 29219 AN: 42764

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 18470 AN: 25836

East Asian (EAS) AF: 0.859 AC: 33677 AN: 39220

South Asian (SAS) AF: 0.744 AC: 62916 AN: 84524

European-Finnish (FIN) AF: 0.771 AC: 40797 AN: 52940

Middle Eastern (MID) AF: 0.732 AC: 4159 AN: 5684

European-Non Finnish (NFE) AF: 0.688 AC: 748017 AN: 1087482

Other (OTH) AF: 0.690 AC: 40630 AN: 58874

GnomAD4 genome AF: 0.693 AC: 101440 AN: 146346 Hom.: 34471 Cov.: 31 AF XY: 0.697 AC XY: 49903 AN XY: 71548

African (AFR) AF: 0.617 AC: 22285 AN: 36140

American (AMR) AF: 0.703 AC: 10587 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2441 AN: 3464

East Asian (EAS) AF: 0.849 AC: 4374 AN: 5154

South Asian (SAS) AF: 0.755 AC: 3634 AN: 4814

European-Finnish (FIN) AF: 0.769 AC: 8092 AN: 10516

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.704 AC: 47849 AN: 67924

Other (OTH) AF: 0.674 AC: 1388 AN: 2060

Alfa AF: 0.592 Hom.: 13290

Bravo AF: 0.651

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	Congenital contractural arachnodactyly (6)
-	-	6	not specified (6)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	Macular degeneration, early-onset (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.41
DANN	Benign	0.74
PhyloP100		0.92
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.034
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: rs27713; hg19: chr5-127640783;