19-8086355-G-C

Variant names:

• chr19-8086355-G-C
• rs8103000
• NM_032447.5:c.6755-30C>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.6755-30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,563,828 control chromosomes in the GnomAD database, including 68,834 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 0.31 (7489 hom., cov: 31)
  • Exomes 𝑓: 0.29 (61345 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.6755-30C>G		intron_variant	Intron 54 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.6755-30C>G		intron_variant	Intron 54 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.6755-30C>G		intron_variant	Intron 53 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.6755-30C>G		intron_variant	Intron 54 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.6881-30C>G		intron_variant	Intron 54 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46940 AN: 151854 Hom.: 7469 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.308

GnomAD2 exomes AF: 0.317 AC: 69195 AN: 218562 AF XY: 0.308

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.402

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.291 AC: 410609 AN: 1411860 Hom.: 61345 Cov.: 30 AF XY: 0.289 AC XY: 201537 AN XY: 696790

African (AFR) AF: 0.327 AC: 10489 AN: 32100

American (AMR) AF: 0.450 AC: 18847 AN: 41914

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 5561 AN: 24048

East Asian (EAS) AF: 0.398 AC: 14913 AN: 37424

South Asian (SAS) AF: 0.283 AC: 22745 AN: 80394

European-Finnish (FIN) AF: 0.283 AC: 14659 AN: 51800

Middle Eastern (MID) AF: 0.225 AC: 1253 AN: 5562

European-Non Finnish (NFE) AF: 0.282 AC: 305091 AN: 1080390

Other (OTH) AF: 0.293 AC: 17051 AN: 58228

GnomAD4 genome AF: 0.309 AC: 46990 AN: 151968 Hom.: 7489 Cov.: 31 AF XY: 0.309 AC XY: 22974 AN XY: 74268

African (AFR) AF: 0.331 AC: 13725 AN: 41442

American (AMR) AF: 0.390 AC: 5958 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2037 AN: 5162

South Asian (SAS) AF: 0.276 AC: 1329 AN: 4814

European-Finnish (FIN) AF: 0.290 AC: 3059 AN: 10566

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19259 AN: 67922

Other (OTH) AF: 0.305 AC: 643 AN: 2108

Alfa AF: 0.204 Hom.: 641

Bravo AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.69
DANN	Benign	0.51
PhyloP100		-0.61
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: rs8103000; hg19: chr19-8151239; COSMIC: COSV107213145; COSMIC: COSV107213145;