rs7252584

Variant names:

• chr19-8142357-C-G
• rs7252584
• NM_032447.5:c.542-220G>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.542-220G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,100 control chromosomes in the GnomAD database, including 1,513 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 0.14 (1513 hom., cov: 31)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 5 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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 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.542-220G>C		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.542-220G>C		intron	N/A	NP_001308360.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	ENST00000600128.6	TSL:1 MANE Select	c.542-220G>C		intron	N/A	ENSP00000470498.1
	FBN3	ENST00000270509.6	TSL:1	c.542-220G>C		intron	N/A	ENSP00000270509.2
	FBN3	ENST00000601739.5	TSL:1	c.542-220G>C		intron	N/A	ENSP00000472324.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20979 AN: 151980 Hom.: 1511 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.138 AC: 20987 AN: 152100 Hom.: 1513 Cov.: 31 AF XY: 0.141 AC XY: 10502 AN XY: 74358

African (AFR) AF: 0.100 AC: 4157 AN: 41510

American (AMR) AF: 0.173 AC: 2646 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3470

East Asian (EAS) AF: 0.189 AC: 975 AN: 5154

South Asian (SAS) AF: 0.148 AC: 716 AN: 4830

European-Finnish (FIN) AF: 0.159 AC: 1678 AN: 10560

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9705 AN: 67992

Other (OTH) AF: 0.152 AC: 322 AN: 2112

Alfa AF: 0.133 Hom.: 177

Bravo AF: 0.137

Asia WGS AF: 0.179 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.0
DANN	Benign	0.77
PhyloP100		-0.13
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: rs7252584; hg19: chr19-8207241;