rs3865464

Variant names:

• chr19-8103456-T-A
• rs3865464
• NM_032447.5:c.4939+106A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-8103456-T-A
• chr19-8103456-T-C

Variant summary

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

The NM_032447.5(FBN3):​c.4939+106A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,195,472 control chromosomes in the GnomAD database, including 7,673 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 0.096 (796 hom., cov: 30)
  • Exomes 𝑓: 0.11 (6877 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.4939+106A>T		intron_variant	Intron 39 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.4939+106A>T		intron_variant	Intron 39 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.4939+106A>T		intron_variant	Intron 38 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.4939+106A>T		intron_variant	Intron 39 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.5065+106A>T		intron_variant	Intron 39 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.0959 AC: 14577 AN: 151928 Hom.: 790 Cov.: 30

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.111 AC: 115743 AN: 1043426 Hom.: 6877 AF XY: 0.111 AC XY: 58320 AN XY: 526018

African (AFR) AF: 0.0573 AC: 1425 AN: 24864

American (AMR) AF: 0.115 AC: 3519 AN: 30662

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 3214 AN: 17672

East Asian (EAS) AF: 0.196 AC: 7046 AN: 35980

South Asian (SAS) AF: 0.100 AC: 6543 AN: 65240

European-Finnish (FIN) AF: 0.0595 AC: 2603 AN: 43756

Middle Eastern (MID) AF: 0.142 AC: 462 AN: 3252

European-Non Finnish (NFE) AF: 0.110 AC: 85684 AN: 776916

Other (OTH) AF: 0.116 AC: 5247 AN: 45084

GnomAD4 genome AF: 0.0960 AC: 14598 AN: 152046 Hom.: 796 Cov.: 30 AF XY: 0.0931 AC XY: 6921 AN XY: 74308

African (AFR) AF: 0.0613 AC: 2544 AN: 41496

American (AMR) AF: 0.110 AC: 1679 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3472

East Asian (EAS) AF: 0.160 AC: 827 AN: 5160

South Asian (SAS) AF: 0.0981 AC: 472 AN: 4810

European-Finnish (FIN) AF: 0.0503 AC: 533 AN: 10594

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7649 AN: 67958

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.0441 Hom.: 44

Bravo AF: 0.100

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.54
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3865464; hg19: chr19-8168340;