19-8085778-G-A

Variant names:

• chr19-8085778-G-A
• rs7260399
• NM_032447.5:c.6881-209C>T

Variant summary

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

The NM_032447.5(FBN3):​c.6881-209C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,632 control chromosomes in the GnomAD database, including 23,631 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 0.55 (23631 hom., cov: 29)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	NM_032447.5	MANE Select	c.6881-209C>T		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.6881-209C>T		intron	N/A	NP_001308360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	ENST00000600128.6	TSL:1 MANE Select	c.6881-209C>T		intron	N/A	ENSP00000470498.1
	FBN3	ENST00000270509.6	TSL:1	c.6881-209C>T		intron	N/A	ENSP00000270509.2
	FBN3	ENST00000601739.5	TSL:1	c.6881-209C>T		intron	N/A	ENSP00000472324.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83105 AN: 151518 Hom.: 23585 Cov.: 29

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.549 AC: 83212 AN: 151632 Hom.: 23631 Cov.: 29 AF XY: 0.547 AC XY: 40511 AN XY: 74082

African (AFR) AF: 0.692 AC: 28609 AN: 41334

American (AMR) AF: 0.569 AC: 8678 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3468

East Asian (EAS) AF: 0.463 AC: 2352 AN: 5078

South Asian (SAS) AF: 0.421 AC: 2018 AN: 4798

European-Finnish (FIN) AF: 0.506 AC: 5334 AN: 10546

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33230 AN: 67838

Other (OTH) AF: 0.529 AC: 1117 AN: 2110

Alfa AF: 0.507 Hom.: 6702

Bravo AF: 0.560

Asia WGS AF: 0.463 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.80
PhyloP100		-1.6
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: rs7260399; hg19: chr19-8150662;