rs374748

chr5-128363682-G-Achr5-128363682-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.2428+918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,156 control chromosomes in the GnomAD database, including 56,305 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 0.86 (56305 hom., cov: 32)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN2	NM_001999.4	c.2428+918C>T		intron_variant		ENST00000262464.9
FBN2	XM_017009228.3	c.2275+918C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000262464.9	c.2428+918C>T		intron_variant		1	NM_001999.4	P1
FBN2	ENST00000508989.5	c.2329+918C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130200 AN: 152038 Hom.: 56261 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.856 AC: 130299 AN: 152156 Hom.: 56305 Cov.: 32 AF XY: 0.860 AC XY: 63954 AN XY: 74404

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.866

Alfa AF: 0.896 Hom.: 96965

Bravo AF: 0.845

Asia WGS AF: 0.949 AC: 3300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.32
Dann	Benign	0.30

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: rs374748; hg19: chr5-127699375;