chr19-8070286-A-G

Variant names:

• chr19-8070286-A-G
• rs10424096
• NM_032447.5:c.8088+1762T>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.8088+1762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,096 control chromosomes in the GnomAD database, including 9,686 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 0.28 (9686 hom., cov: 32)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.8088+1762T>C		intron_variant	Intron 63 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.8088+1762T>C		intron_variant	Intron 63 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.8088+1762T>C		intron_variant	Intron 62 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.8088+1762T>C		intron_variant	Intron 63 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.8214+1762T>C		intron_variant	Intron 63 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42696 AN: 151978 Hom.: 9648 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.281 AC: 42788 AN: 152096 Hom.: 9686 Cov.: 32 AF XY: 0.286 AC XY: 21272 AN XY: 74370

African (AFR) AF: 0.612 AC: 25377 AN: 41442

American (AMR) AF: 0.288 AC: 4398 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1450 AN: 5174

South Asian (SAS) AF: 0.338 AC: 1626 AN: 4816

European-Finnish (FIN) AF: 0.187 AC: 1975 AN: 10582

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0987 AC: 6713 AN: 68022

Other (OTH) AF: 0.256 AC: 541 AN: 2110

Alfa AF: 0.175 Hom.: 964

Bravo AF: 0.302

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-1.1
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: rs10424096; hg19: chr19-8135170;