rs331079

chr5-128435112-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001999.4(FBN2):c.952+11369C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 152,048 control chromosomes in the GnomAD database, including 1,026 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 0.098 (1026 hom., cov: 31)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.687

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN2	NM_001999.4	c.952+11369C>G		intron_variant		ENST00000262464.9
FBN2	XM_017009228.3	c.952+11369C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000262464.9	c.952+11369C>G		intron_variant		1	NM_001999.4	P1
FBN2	ENST00000508053.6	c.952+11369C>G		intron_variant		5
FBN2	ENST00000508989.5	c.853+11369C>G		intron_variant		2
FBN2	ENST00000703787.1	n.659+11369C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14883 AN: 151930 Hom.: 1022 Cov.: 31

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.0979 AC: 14893 AN: 152048 Hom.: 1026 Cov.: 31 AF XY: 0.0991 AC XY: 7364 AN XY: 74344

Gnomad4 AFR AF: 0.0434

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0621

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0947 Hom.: 121

Bravo AF: 0.113

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	14
Dann	Benign	0.68

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: rs331079; hg19: chr5-127770805; COSMIC: COSV52501922;