rs12981294

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-8091337-A-G
• chr19-8091337-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032447.5(FBN3):​c.6031+128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,287,608 control chromosomes in the GnomAD database, including 32,124 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 0.20 (3113 hom., cov: 32)
  • Exomes 𝑓: 0.22 (29011 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	NM_032447.5	MANE Select	c.6031+128T>C		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.6031+128T>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.6031+128T>C		intron	N/A	ENSP00000470498.1
	FBN3	ENST00000270509.6	TSL:1	c.6031+128T>C		intron	N/A	ENSP00000270509.2
	FBN3	ENST00000601739.5	TSL:1	c.6031+128T>C		intron	N/A	ENSP00000472324.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30114 AN: 151214 Hom.: 3101 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.224 AC: 254291 AN: 1136280 Hom.: 29011 AF XY: 0.224 AC XY: 126979 AN XY: 567724

African (AFR) AF: 0.145 AC: 3671 AN: 25364

American (AMR) AF: 0.195 AC: 5949 AN: 30492

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 5044 AN: 18812

East Asian (EAS) AF: 0.140 AC: 5303 AN: 37858

South Asian (SAS) AF: 0.207 AC: 13668 AN: 65916

European-Finnish (FIN) AF: 0.201 AC: 8944 AN: 44468

Middle Eastern (MID) AF: 0.243 AC: 1180 AN: 4854

European-Non Finnish (NFE) AF: 0.232 AC: 199742 AN: 859762

Other (OTH) AF: 0.221 AC: 10790 AN: 48754

GnomAD4 genome AF: 0.199 AC: 30156 AN: 151328 Hom.: 3113 Cov.: 32 AF XY: 0.197 AC XY: 14597 AN XY: 73978

African (AFR) AF: 0.150 AC: 6090 AN: 40716

American (AMR) AF: 0.202 AC: 3072 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3472

East Asian (EAS) AF: 0.134 AC: 696 AN: 5184

South Asian (SAS) AF: 0.195 AC: 940 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2067 AN: 10606

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15720 AN: 67992

Other (OTH) AF: 0.208 AC: 437 AN: 2096

Alfa AF: 0.222 Hom.: 5671

Bravo AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		0.013
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: rs12981294; hg19: chr19-8156221; COSMIC: COSV107212434; COSMIC: COSV107212434;