19-8086534-A-G

Variant names:

• chr19-8086534-A-G
• rs8105886
• NM_032447.5:c.6755-209T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032447.5(FBN3):​c.6755-209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 149,142 control chromosomes in the GnomAD database, including 66,746 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 0.95 (66746 hom., cov: 24)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.6755-209T>C		intron_variant	Intron 54 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.6755-209T>C		intron_variant	Intron 54 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.6755-209T>C		intron_variant	Intron 53 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.6755-209T>C		intron_variant	Intron 54 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.6881-209T>C		intron_variant	Intron 54 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.946 AC: 140952 AN: 149050 Hom.: 66699 Cov.: 24

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.955

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.946 AC: 141043 AN: 149142 Hom.: 66746 Cov.: 24 AF XY: 0.947 AC XY: 68797 AN XY: 72628

Gnomad4 AFR AF: 0.959

Gnomad4 AMR AF: 0.955

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.935

Gnomad4 FIN AF: 0.979

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.936

Alfa AF: 0.943 Hom.: 7897

Bravo AF: 0.946

Asia WGS AF: 0.894 AC: 3107 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs8105886; hg19: chr19-8151418;