19-8071514-T-C

Variant names:

• chr19-8071514-T-C
• rs17261710
• NM_032447.5:c.8088+534A>G

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+534A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,192 control chromosomes in the GnomAD database, including 1,458 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 0.13 (1458 hom., cov: 32)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.8088+534A>G		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+534A>G		intron_variant	Intron 63 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.8088+534A>G		intron_variant	Intron 62 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.8088+534A>G		intron_variant	Intron 63 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.8214+534A>G		intron_variant	Intron 63 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19346 AN: 152074 Hom.: 1454 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.127 AC: 19355 AN: 152192 Hom.: 1458 Cov.: 32 AF XY: 0.129 AC XY: 9580 AN XY: 74418

African (AFR) AF: 0.0403 AC: 1673 AN: 41550

American (AMR) AF: 0.126 AC: 1923 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3470

East Asian (EAS) AF: 0.140 AC: 724 AN: 5172

South Asian (SAS) AF: 0.137 AC: 663 AN: 4822

European-Finnish (FIN) AF: 0.169 AC: 1790 AN: 10592

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11674 AN: 67988

Other (OTH) AF: 0.124 AC: 262 AN: 2106

Alfa AF: 0.153 Hom.: 5093

Bravo AF: 0.119

Asia WGS AF: 0.126 AC: 440 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	5.8
DANN	Benign	0.84
PhyloP100		-0.075
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: rs17261710; hg19: chr19-8136398;