19-8094040-C-G

Variant names:

• chr19-8094040-C-G
• rs12151028
• NM_032447.5:c.5905+406G>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.5905+406G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,112 control chromosomes in the GnomAD database, including 1,397 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 0.12 (1397 hom., cov: 33)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	NM_032447.5	MANE Select	c.5905+406G>C		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.5905+406G>C		intron	N/A	NP_001308360.1	Q75N90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	ENST00000600128.6	TSL:1 MANE Select	c.5905+406G>C		intron	N/A	ENSP00000470498.1	Q75N90
	FBN3	ENST00000270509.6	TSL:1	c.5905+406G>C		intron	N/A	ENSP00000270509.2	Q75N90
	FBN3	ENST00000601739.5	TSL:1	c.5905+406G>C		intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17952 AN: 151994 Hom.: 1394 Cov.: 33

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.0925

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.118 AC: 17963 AN: 152112 Hom.: 1397 Cov.: 33 AF XY: 0.121 AC XY: 9025 AN XY: 74344

African (AFR) AF: 0.0323 AC: 1341 AN: 41506

American (AMR) AF: 0.207 AC: 3168 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.262 AC: 1352 AN: 5160

South Asian (SAS) AF: 0.109 AC: 527 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2057 AN: 10570

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8816 AN: 67998

Other (OTH) AF: 0.123 AC: 260 AN: 2106

Alfa AF: 0.0657 Hom.: 69

Bravo AF: 0.118

Asia WGS AF: 0.156 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.77
PhyloP100		0.59
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: rs12151028; hg19: chr19-8158924;