rs2086149

Variant names:

• chr19-8112736-C-T
• rs2086149
• NM_032447.5:c.3839-637G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032447.5(FBN3):​c.3839-637G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,116 control chromosomes in the GnomAD database, including 10,168 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 0.36 (10168 hom., cov: 33)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 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.3839-637G>A		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.3839-637G>A		intron	N/A	NP_001308360.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	ENST00000600128.6	TSL:1 MANE Select	c.3839-637G>A		intron	N/A	ENSP00000470498.1
	FBN3	ENST00000270509.6	TSL:1	c.3839-637G>A		intron	N/A	ENSP00000270509.2
	FBN3	ENST00000601739.5	TSL:1	c.3839-637G>A		intron	N/A	ENSP00000472324.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53968 AN: 151998 Hom.: 10152 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.355 AC: 54021 AN: 152116 Hom.: 10168 Cov.: 33 AF XY: 0.366 AC XY: 27197 AN XY: 74354

African (AFR) AF: 0.444 AC: 18424 AN: 41480

American (AMR) AF: 0.352 AC: 5381 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3472

East Asian (EAS) AF: 0.368 AC: 1910 AN: 5188

South Asian (SAS) AF: 0.536 AC: 2585 AN: 4824

European-Finnish (FIN) AF: 0.426 AC: 4496 AN: 10564

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19068 AN: 67984

Other (OTH) AF: 0.315 AC: 665 AN: 2112

Alfa AF: 0.300 Hom.: 12033

Bravo AF: 0.349

Asia WGS AF: 0.462 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.86
PhyloP100		-1.4
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: rs2086149; hg19: chr19-8177620;