19-8066965-T-C

Variant names:

• chr19-8066965-T-C
• rs12972954
• NM_032447.5:c.8089-705A>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.8089-705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,754 control chromosomes in the GnomAD database, including 27,833 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 0.60 (27833 hom., cov: 30)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 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.8089-705A>G		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.8089-705A>G		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.8089-705A>G		intron	N/A	ENSP00000470498.1	Q75N90
	FBN3	ENST00000270509.6	TSL:1	c.8089-705A>G		intron	N/A	ENSP00000270509.2	Q75N90
	FBN3	ENST00000601739.5	TSL:1	c.8089-705A>G		intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91143 AN: 151634 Hom.: 27817 Cov.: 30

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.601 AC: 91195 AN: 151754 Hom.: 27833 Cov.: 30 AF XY: 0.601 AC XY: 44556 AN XY: 74140

African (AFR) AF: 0.558 AC: 23088 AN: 41378

American (AMR) AF: 0.489 AC: 7433 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2520 AN: 3470

East Asian (EAS) AF: 0.772 AC: 3983 AN: 5158

South Asian (SAS) AF: 0.745 AC: 3579 AN: 4804

European-Finnish (FIN) AF: 0.581 AC: 6091 AN: 10486

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42557 AN: 67938

Other (OTH) AF: 0.604 AC: 1275 AN: 2112

Alfa AF: 0.562 Hom.: 3536

Bravo AF: 0.591

Asia WGS AF: 0.693 AC: 2414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.38
PhyloP100		-2.6
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: rs12972954; hg19: chr19-8131849;