5-128305169-A-G

Variant names:

• chr5-128305169-A-G
• rs27855
• NM_001999.4:c.5675-87T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001999.4(FBN2):​c.5675-87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,132,668 control chromosomes in the GnomAD database, including 196,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (22235 hom., cov: 33)
  • Exomes 𝑓: 0.59 (174468 hom.)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.51

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 5-128305169-A-G is Benign according to our data. Variant chr5-128305169-A-G is described in ClinVar as [Benign]. Clinvar id is 671004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.5675-87T>C		intron_variant	Intron 44 of 64	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.5522-87T>C		intron_variant	Intron 43 of 63		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.5675-87T>C		intron_variant	Intron 44 of 64	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000703783.1	n.2459-87T>C		intron_variant	Intron 19 of 37
FBN2	ENST00000703785.1	n.2378-87T>C		intron_variant	Intron 18 of 26

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76318 AN: 151976 Hom.: 22225 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.588 AC: 576900 AN: 980574 Hom.: 174468 AF XY: 0.593 AC XY: 297342 AN XY: 501322

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.645

Gnomad4 FIN exome AF: 0.712

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.502 AC: 76341 AN: 152094 Hom.: 22235 Cov.: 33 AF XY: 0.513 AC XY: 38115 AN XY: 74328

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.524

Alfa AF: 0.592 Hom.: 57282

Bravo AF: 0.472

Asia WGS AF: 0.696 AC: 2416 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs27855; hg19: chr5-127640861;