19-8142837-G-A

Variant names:

• chr19-8142837-G-A
• rs7256533
• NM_032447.5:c.542-700C>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.542-700C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.37 (9115 hom., cov: 17)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.542-700C>T		intron_variant	Intron 6 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.542-700C>T		intron_variant	Intron 6 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.542-700C>T		intron_variant	Intron 5 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.542-700C>T		intron_variant	Intron 6 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.542-700C>T		intron_variant	Intron 5 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 46378 AN: 124440 Hom.: 9124 Cov.: 17

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.373 AC: 46379 AN: 124492 Hom.: 9115 Cov.: 17 AF XY: 0.370 AC XY: 21663 AN XY: 58614

African (AFR) AF: 0.234 AC: 7360 AN: 31450

American (AMR) AF: 0.371 AC: 4090 AN: 11036

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1267 AN: 3228

East Asian (EAS) AF: 0.214 AC: 896 AN: 4180

South Asian (SAS) AF: 0.229 AC: 870 AN: 3794

European-Finnish (FIN) AF: 0.467 AC: 3142 AN: 6734

Middle Eastern (MID) AF: 0.366 AC: 90 AN: 246

European-Non Finnish (NFE) AF: 0.452 AC: 27724 AN: 61376

Other (OTH) AF: 0.385 AC: 629 AN: 1634

Alfa AF: 0.403 Hom.: 4345

Bravo AF: 0.346

Asia WGS AF: 0.241 AC: 839 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.43
PhyloP100		-1.3
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: rs7256533; hg19: chr19-8207721;