rs10445638

Variant names:

• chr19-8108544-C-T
• rs10445638
• NM_032447.5:c.4619-306G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032447.5(FBN3):​c.4619-306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 151,970 control chromosomes in the GnomAD database, including 1,284 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 0.11 (1284 hom., cov: 31)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• 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 (EAS) allele frequency at 95% confidence interval = 0.253 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.4619-306G>A		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.4619-306G>A		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.4619-306G>A		intron	N/A	ENSP00000470498.1	Q75N90
	FBN3	ENST00000270509.6	TSL:1	c.4619-306G>A		intron	N/A	ENSP00000270509.2	Q75N90
	FBN3	ENST00000601739.5	TSL:1	c.4619-306G>A		intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17149 AN: 151852 Hom.: 1282 Cov.: 31

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.113 AC: 17155 AN: 151970 Hom.: 1284 Cov.: 31 AF XY: 0.115 AC XY: 8560 AN XY: 74252

African (AFR) AF: 0.0311 AC: 1290 AN: 41466

American (AMR) AF: 0.201 AC: 3068 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1366 AN: 5168

South Asian (SAS) AF: 0.106 AC: 510 AN: 4812

European-Finnish (FIN) AF: 0.166 AC: 1757 AN: 10568

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

European-Non Finnish (NFE) AF: 0.125 AC: 8487 AN: 67930

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.118 Hom.: 1973

Bravo AF: 0.114

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.67
PhyloP100		0.091
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: rs10445638; hg19: chr19-8173428;