19-8065536-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032447.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	NM_032447.5	MANE Select	c.*383G>C		3_prime_UTR	Exon 64 of 64	NP_115823.3
	FBN3	NM_001321431.2		c.*383G>C		3_prime_UTR	Exon 64 of 64	NP_001308360.1	Q75N90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	ENST00000600128.6	TSL:1 MANE Select	c.*383G>C		3_prime_UTR	Exon 64 of 64	ENSP00000470498.1	Q75N90
	FBN3	ENST00000270509.6	TSL:1	c.*383G>C		3_prime_UTR	Exon 63 of 63	ENSP00000270509.2	Q75N90
	FBN3	ENST00000601739.5	TSL:1	c.*383G>C		3_prime_UTR	Exon 64 of 64	ENSP00000472324.1	Q75N90

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

African (AFR) AF: 0.0341 AC: 86 AN: 2522

American (AMR) AF: 0.123 AC: 254 AN: 2062

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 372 AN: 2604

East Asian (EAS) AF: 0.394 AC: 1862 AN: 4730

South Asian (SAS) AF: 0.173 AC: 144 AN: 832

European-Finnish (FIN) AF: 0.184 AC: 719 AN: 3898

Middle Eastern (MID) AF: 0.182 AC: 70 AN: 384

European-Non Finnish (NFE) AF: 0.158 AC: 6810 AN: 43080

Other (OTH) AF: 0.158 AC: 723 AN: 4586

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

African (AFR) AF: 0.0425 AC: 1765 AN: 41576

American (AMR) AF: 0.125 AC: 1911 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2199 AN: 5168

South Asian (SAS) AF: 0.191 AC: 921 AN: 4834

European-Finnish (FIN) AF: 0.212 AC: 2245 AN: 10590

Middle Eastern (MID) AF: 0.179 AC: 52 AN: 290

European-Non Finnish (NFE) AF: 0.170 AC: 11545 AN: 67988

Other (OTH) AF: 0.137 AC: 289 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.67
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2287937; hg19: chr19-8130420;