5-128495572-G-C

Position:

• chr5-128495572-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.628+23701C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 151,970 control chromosomes in the GnomAD database, including 705 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 0.087 (705 hom., cov: 32)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4	c.628+23701C>G		intron_variant		ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.628+23701C>G		intron_variant			XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.628+23701C>G		intron_variant		1	NM_001999.4	ENSP00000262464	P1

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13237 AN: 151854 Hom.: 700 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.0889

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

GnomAD4 genome AF: 0.0873 AC: 13274 AN: 151970 Hom.: 705 Cov.: 32 AF XY: 0.0891 AC XY: 6620 AN XY: 74266

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.0534

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0757

Gnomad4 NFE AF: 0.0578

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0697 Hom.: 60

Bravo AF: 0.0876

Asia WGS AF: 0.166 AC: 573 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.28
DANN	Benign	0.32

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: rs10478813; hg19: chr5-127831265;