rs17202517

Variant names:

• chr19-8083417-G-A
• rs17202517
• NM_032447.5:c.7088-45C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-8083417-G-A
• chr19-8083417-G-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.7088-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,603,190 control chromosomes in the GnomAD database, including 39,622 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 0.17 (2771 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36851 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 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.7088-45C>T		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.7088-45C>T		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.7088-45C>T		intron	N/A	ENSP00000470498.1	Q75N90
	FBN3	ENST00000270509.6	TSL:1	c.7088-45C>T		intron	N/A	ENSP00000270509.2	Q75N90
	FBN3	ENST00000601739.5	TSL:1	c.7088-45C>T		intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25802 AN: 152024 Hom.: 2768 Cov.: 32

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.188 AC: 46367 AN: 247026 AF XY: 0.192

Gnomad AFR exome AF: 0.0414

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.218 AC: 315838 AN: 1451048 Hom.: 36851 Cov.: 32 AF XY: 0.217 AC XY: 156446 AN XY: 721958

African (AFR) AF: 0.0380 AC: 1270 AN: 33426

American (AMR) AF: 0.113 AC: 5059 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4381 AN: 26048

East Asian (EAS) AF: 0.113 AC: 4495 AN: 39622

South Asian (SAS) AF: 0.145 AC: 12448 AN: 86120

European-Finnish (FIN) AF: 0.271 AC: 13620 AN: 50332

Middle Eastern (MID) AF: 0.153 AC: 881 AN: 5756

European-Non Finnish (NFE) AF: 0.237 AC: 261934 AN: 1105022

Other (OTH) AF: 0.196 AC: 11750 AN: 60052

GnomAD4 genome AF: 0.170 AC: 25805 AN: 152142 Hom.: 2771 Cov.: 32 AF XY: 0.170 AC XY: 12665 AN XY: 74366

African (AFR) AF: 0.0463 AC: 1922 AN: 41526

American (AMR) AF: 0.135 AC: 2062 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3470

East Asian (EAS) AF: 0.125 AC: 647 AN: 5178

South Asian (SAS) AF: 0.152 AC: 736 AN: 4828

European-Finnish (FIN) AF: 0.272 AC: 2876 AN: 10582

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16295 AN: 67964

Other (OTH) AF: 0.155 AC: 328 AN: 2112

Alfa AF: 0.205 Hom.: 5971

Bravo AF: 0.151

Asia WGS AF: 0.131 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.39
PhyloP100		-0.078
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs17202517; hg19: chr19-8148301; COSMIC: COSV54459161; COSMIC: COSV54459161;