chr3-13629276-T-C

Position:

• chr3-13629276-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001004019.2(FBLN2):​c.2826T>C​(p.Phe942Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,610,110 control chromosomes in the GnomAD database, including 379,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39293 hom., cov: 36)
  • Exomes 𝑓: 0.68 (340242 hom.)
• Consequence: FBLN2 NM_001004019.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.338

Genes affected

FBLN2 (HGNC:3601): (fibulin 2) This gene encodes an extracellular matrix protein, which belongs to the fibulin family. This protein binds various extracellular ligands and calcium. It may play a role during organ development, in particular, during the differentiation of heart, skeletal and neuronal structures. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 3-13629276-T-C is Benign according to our data. Variant chr3-13629276-T-C is described in ClinVar as [Benign]. Clinvar id is 1342035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.338 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLN2	NM_001004019.2	c.2826T>C	p.Phe942Phe	synonymous_variant	13/18	ENST00000404922.8	NP_001004019.1
FBLN2	NM_001165035.2	c.2826T>C	p.Phe942Phe	synonymous_variant	13/18		NP_001158507.1
FBLN2	NM_001998.3	c.2685T>C	p.Phe895Phe	synonymous_variant	12/17		NP_001989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLN2	ENST00000404922.8	c.2826T>C	p.Phe942Phe	synonymous_variant	13/18	5	NM_001004019.2	ENSP00000384169.3
FBLN2	ENST00000295760.11	c.2685T>C	p.Phe895Phe	synonymous_variant	12/17	1		ENSP00000295760.7
FBLN2	ENST00000492059.5	c.2826T>C	p.Phe942Phe	synonymous_variant	13/18	2		ENSP00000420042.1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108743 AN: 152092 Hom.: 39268 Cov.: 36

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.702

GnomAD3 exomes AF: 0.729 AC: 177123 AN: 242876 Hom.: 65921 AF XY: 0.723 AC XY: 95693 AN XY: 132282

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.851

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.984

Gnomad SAS exome AF: 0.756

Gnomad FIN exome AF: 0.718

Gnomad NFE exome AF: 0.654

Gnomad OTH exome AF: 0.710

GnomAD4 exome AF: 0.679 AC: 990128 AN: 1457900 Hom.: 340242 Cov.: 69 AF XY: 0.680 AC XY: 492868 AN XY: 725042

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.844

Gnomad4 ASJ exome AF: 0.595

Gnomad4 EAS exome AF: 0.989

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.719

Gnomad4 NFE exome AF: 0.653

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.715 AC: 108819 AN: 152210 Hom.: 39293 Cov.: 36 AF XY: 0.721 AC XY: 53663 AN XY: 74422

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.705

Alfa AF: 0.670 Hom.: 42684

Bravo AF: 0.722

Asia WGS AF: 0.883 AC: 3072 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 15, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.1
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4684968; hg19: chr3-13670776;