rs12162237

Variant names:

• chr19-8142186-G-A
• rs12162237
• NM_032447.5:c.542-49C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-8142186-G-A
• chr19-8142186-G-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.542-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,484,270 control chromosomes in the GnomAD database, including 181,385 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 0.53 (22400 hom., cov: 32)
  • Exomes 𝑓: 0.48 (158985 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.664 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.542-49C>T		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.542-49C>T		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.542-49C>T		intron	N/A	ENSP00000470498.1	Q75N90
	FBN3	ENST00000270509.6	TSL:1	c.542-49C>T		intron	N/A	ENSP00000270509.2	Q75N90
	FBN3	ENST00000601739.5	TSL:1	c.542-49C>T		intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81240 AN: 151940 Hom.: 22372 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.521

GnomAD2 exomes AF: 0.531 AC: 86682 AN: 163326 AF XY: 0.535

Gnomad AFR exome AF: 0.667

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.490

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.485 AC: 645915 AN: 1332212 Hom.: 158985 Cov.: 21 AF XY: 0.490 AC XY: 322560 AN XY: 657818

African (AFR) AF: 0.671 AC: 20627 AN: 30752

American (AMR) AF: 0.575 AC: 21338 AN: 37078

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 11917 AN: 23900

East Asian (EAS) AF: 0.503 AC: 18104 AN: 35986

South Asian (SAS) AF: 0.680 AC: 53117 AN: 78134

European-Finnish (FIN) AF: 0.436 AC: 16638 AN: 38184

Middle Eastern (MID) AF: 0.598 AC: 3293 AN: 5508

European-Non Finnish (NFE) AF: 0.460 AC: 472404 AN: 1026868

Other (OTH) AF: 0.510 AC: 28477 AN: 55802

GnomAD4 genome AF: 0.535 AC: 81326 AN: 152058 Hom.: 22400 Cov.: 32 AF XY: 0.537 AC XY: 39922 AN XY: 74312

African (AFR) AF: 0.662 AC: 27453 AN: 41466

American (AMR) AF: 0.561 AC: 8575 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2564 AN: 5156

South Asian (SAS) AF: 0.684 AC: 3304 AN: 4832

European-Finnish (FIN) AF: 0.455 AC: 4818 AN: 10592

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31293 AN: 67948

Other (OTH) AF: 0.525 AC: 1108 AN: 2112

Alfa AF: 0.500 Hom.: 3684

Bravo AF: 0.544

Asia WGS AF: 0.637 AC: 2214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		0.034
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12162237; hg19: chr19-8207070; COSMIC: COSV54470205;