rs3813779

Variant names:

• chr19-8109766-A-G
• rs3813779
• NM_032447.5:c.4334-13T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-8109766-A-G
• chr19-8109766-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032447.5(FBN3):​c.4334-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,459,034 control chromosomes in the GnomAD database, including 200,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19373 hom., cov: 32)
  • Exomes 𝑓: 0.52 (181156 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.196
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 19-8109766-A-G is Benign according to our data. Variant chr19-8109766-A-G is described in ClinVar as Benign. ClinVar VariationId is 1598940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.4334-13T>C		intron_variant	Intron 34 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.4334-13T>C		intron_variant	Intron 34 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.4334-13T>C		intron_variant	Intron 33 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.4334-13T>C		intron_variant	Intron 34 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.4460-13T>C		intron_variant	Intron 34 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74272 AN: 151942 Hom.: 19361 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.471

GnomAD2 exomes AF: 0.552 AC: 82867 AN: 150184 AF XY: 0.555

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.686

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.753

Gnomad FIN exome AF: 0.642

Gnomad NFE exome AF: 0.499

Gnomad OTH exome AF: 0.543

GnomAD4 exome AF: 0.521 AC: 681554 AN: 1306974 Hom.: 181156 Cov.: 39 AF XY: 0.524 AC XY: 334065 AN XY: 637026

African (AFR) AF: 0.315 AC: 8836 AN: 28014

American (AMR) AF: 0.662 AC: 15781 AN: 23822

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 8208 AN: 18740

East Asian (EAS) AF: 0.722 AC: 24706 AN: 34218

South Asian (SAS) AF: 0.661 AC: 39950 AN: 60460

European-Finnish (FIN) AF: 0.630 AC: 30376 AN: 48224

Middle Eastern (MID) AF: 0.461 AC: 2367 AN: 5138

European-Non Finnish (NFE) AF: 0.506 AC: 524014 AN: 1035100

Other (OTH) AF: 0.513 AC: 27316 AN: 53258

GnomAD4 genome AF: 0.489 AC: 74315 AN: 152060 Hom.: 19373 Cov.: 32 AF XY: 0.501 AC XY: 37228 AN XY: 74320

African (AFR) AF: 0.331 AC: 13727 AN: 41498

American (AMR) AF: 0.591 AC: 9036 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1558 AN: 3468

East Asian (EAS) AF: 0.763 AC: 3911 AN: 5126

South Asian (SAS) AF: 0.681 AC: 3277 AN: 4812

European-Finnish (FIN) AF: 0.654 AC: 6915 AN: 10580

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.503 AC: 34203 AN: 67984

Other (OTH) AF: 0.474 AC: 998 AN: 2104

Alfa AF: 0.494 Hom.: 25799

Bravo AF: 0.474

Asia WGS AF: 0.659 AC: 2290 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.35
PhyloP100		-0.20
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: rs3813779; hg19: chr19-8174650;