chr19-8091337-A-T

Variant names:

• chr19-8091337-A-T
• rs12981294
• NM_032447.5:c.6031+128T>A

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.6031+128T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000878 in 1,138,494 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: not found (cov: 32)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 0 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=-0.86).

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.6031+128T>A		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.6031+128T>A		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.6031+128T>A		intron	N/A	ENSP00000470498.1	Q75N90
	FBN3	ENST00000270509.6	TSL:1	c.6031+128T>A		intron	N/A	ENSP00000270509.2	Q75N90
	FBN3	ENST00000601739.5	TSL:1	c.6031+128T>A		intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.78e-7 AC: 1 AN: 1138494 Hom.: 0 AF XY: 0.00000176 AC XY: 1 AN XY: 568758

African (AFR) AF: 0.00 AC: 0 AN: 25406

American (AMR) AF: 0.00 AC: 0 AN: 30522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18838

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37880

South Asian (SAS) AF: 0.00 AC: 0 AN: 66004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4862

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 861616

Other (OTH) AF: 0.00 AC: 0 AN: 48832

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.57
PhyloP100		0.013

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: rs12981294; hg19: chr19-8156221;