19-8065536-C-G

Variant names:

• chr19-8065536-C-G
• rs2287937
• NM_032447.5:c.*383G>C

Variant summary

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

The NM_032447.5(FBN3):​c.*383G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 216,934 control chromosomes in the GnomAD database, including 3,165 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 0.14 (2002 hom., cov: 33)
  • Exomes 𝑓: 0.17 (1163 hom.)
• Consequence: FBN3 NM_032447.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798

Genes affected

FBN3 (HGNC:18794): (fibrillin 3) This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.*383G>C		3_prime_UTR_variant	Exon 64 of 64	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128	c.*383G>C		3_prime_UTR_variant	Exon 64 of 64	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509	c.*383G>C		3_prime_UTR_variant	Exon 63 of 63	1		ENSP00000270509.2
FBN3	ENST00000601739	c.*383G>C		3_prime_UTR_variant	Exon 64 of 64	1		ENSP00000472324.1
FBN3	ENST00000651877	c.*383G>C		3_prime_UTR_variant	Exon 64 of 64			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21660 AN: 152118 Hom.: 2007 Cov.: 33

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.171 AC: 11040 AN: 64698 Hom.: 1163 Cov.: 0 AF XY: 0.170 AC XY: 5514 AN XY: 32386

Gnomad4 AFR exome AF: 0.0341

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.142 AC: 21655 AN: 152236 Hom.: 2002 Cov.: 33 AF XY: 0.146 AC XY: 10839 AN XY: 74430

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0733 Hom.: 102

Bravo AF: 0.134

Asia WGS AF: 0.241 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.67

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: rs2287937; hg19: chr19-8130420;