19-8066965-T-G

Variant names:

• chr19-8066965-T-G
• rs12972954
• NM_032447.5:c.8089-705A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032447.5(FBN3):​c.8089-705A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 151,738 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	NM_032447.5	MANE Select	c.8089-705A>C		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.8089-705A>C		intron	N/A	NP_001308360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	ENST00000600128.6	TSL:1 MANE Select	c.8089-705A>C		intron	N/A	ENSP00000470498.1
	FBN3	ENST00000270509.6	TSL:1	c.8089-705A>C		intron	N/A	ENSP00000270509.2
	FBN3	ENST00000601739.5	TSL:1	c.8089-705A>C		intron	N/A	ENSP00000472324.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151738 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151738 Hom.: 0 Cov.: 30 AF XY: 0.0000270 AC XY: 2 AN XY: 74068

African (AFR) AF: 0.00 AC: 0 AN: 41290

American (AMR) AF: 0.00 AC: 0 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 3536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.39
PhyloP100		-2.6

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;