rs586115

Positions:

• chr5-128327183-T-C

Variant summary

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

The NM_001999.4(FBN2):​c.4471+1513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,188 control chromosomes in the GnomAD database, including 3,532 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 0.21 (3532 hom., cov: 32)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4	c.4471+1513A>G		intron_variant		ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.4318+1513A>G		intron_variant			XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.4471+1513A>G		intron_variant		1	NM_001999.4	ENSP00000262464	P1
FBN2	ENST00000703783.1	n.1255+1513A>G		intron_variant, non_coding_transcript_variant
FBN2	ENST00000703785.1	n.1336+1513A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32283 AN: 152070 Hom.: 3528 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.212 AC: 32301 AN: 152188 Hom.: 3532 Cov.: 32 AF XY: 0.206 AC XY: 15353 AN XY: 74408

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.220

Alfa AF: 0.208 Hom.: 409

Bravo AF: 0.225

Asia WGS AF: 0.152 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs586115; hg19: chr5-127662875;