rs1435514

Positions:

• chr5-128506726-C-T

Variant summary

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

The NM_001999.4(FBN2):​c.628+12547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,930 control chromosomes in the GnomAD database, including 22,040 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 0.50 (22040 hom., cov: 32)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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 = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4	c.628+12547G>A		intron_variant		ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.628+12547G>A		intron_variant			XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.628+12547G>A		intron_variant		1	NM_001999.4	ENSP00000262464	P1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75431 AN: 151812 Hom.: 21987 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.497 AC: 75549 AN: 151930 Hom.: 22040 Cov.: 32 AF XY: 0.488 AC XY: 36236 AN XY: 74256

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.449

Alfa AF: 0.450 Hom.: 2172

Bravo AF: 0.509

Asia WGS AF: 0.398 AC: 1384 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.49

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: rs1435514; hg19: chr5-127842419; COSMIC: COSV52502486;