rs17160153

Variant names:

• chr19-8093848-T-C
• rs17160153
• NM_032447.5:c.5905+598A>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.5905+598A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,206 control chromosomes in the GnomAD database, including 235 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 0.023 (235 hom., cov: 33)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.5905+598A>G		intron_variant	Intron 47 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.5905+598A>G		intron_variant	Intron 47 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.5905+598A>G		intron_variant	Intron 46 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.5905+598A>G		intron_variant	Intron 47 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.6031+598A>G		intron_variant	Intron 47 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3459 AN: 152088 Hom.: 232 Cov.: 33

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0228 AC: 3470 AN: 152206 Hom.: 235 Cov.: 33 AF XY: 0.0290 AC XY: 2161 AN XY: 74428

African (AFR) AF: 0.00284 AC: 118 AN: 41538

American (AMR) AF: 0.0663 AC: 1013 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.176 AC: 909 AN: 5176

South Asian (SAS) AF: 0.161 AC: 779 AN: 4824

European-Finnish (FIN) AF: 0.0356 AC: 378 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00246 AC: 167 AN: 67988

Other (OTH) AF: 0.0217 AC: 46 AN: 2116

Alfa AF: 0.00995 Hom.: 8

Bravo AF: 0.0228

Asia WGS AF: 0.171 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.73
PhyloP100		0.91
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: rs17160153; hg19: chr19-8158732;