5-128497163-C-T

Position:

• chr5-128497163-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+22110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,026 control chromosomes in the GnomAD database, including 13,304 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 0.33 (13304 hom., cov: 32)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN2	NM_001999.4	c.628+22110G>A		intron_variant		ENST00000262464.9
FBN2	XM_017009228.3	c.628+22110G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000262464.9	c.628+22110G>A		intron_variant		1	NM_001999.4	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50295 AN: 151908 Hom.: 13253 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.332 AC: 50411 AN: 152026 Hom.: 13304 Cov.: 32 AF XY: 0.327 AC XY: 24322 AN XY: 74320

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.285

Alfa AF: 0.186 Hom.: 5377

Bravo AF: 0.350

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.22

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: rs11960575; hg19: chr5-127832856; COSMIC: COSV52502347;