3-13618397-A-T

Variant names:

• chr3-13618397-A-T
• rs4596126
• NM_001004019.2:c.1939+112A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004019.2(FBLN2):​c.1939+112A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 800,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: FBLN2 NM_001004019.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.93
• Publications: 0 publications found

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]

SNORA93 (HGNC:50397): (small nucleolar RNA, H/ACA box 93)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBLN2	NM_001004019.2	c.1939+112A>T		intron_variant	Intron 6 of 17	ENST00000404922.8	NP_001004019.1
SNORA93	NR_132775.1	n.17A>T		non_coding_transcript_exon_variant	Exon 1 of 1
FBLN2	NM_001165035.2	c.1939+112A>T		intron_variant	Intron 6 of 17		NP_001158507.1
FBLN2	NM_001998.3	c.1939+112A>T		intron_variant	Intron 6 of 16		NP_001989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBLN2	ENST00000404922.8	c.1939+112A>T		intron_variant	Intron 6 of 17	5	NM_001004019.2	ENSP00000384169.3
FBLN2	ENST00000295760.11	c.1939+112A>T		intron_variant	Intron 6 of 16	1		ENSP00000295760.7
FBLN2	ENST00000492059.5	c.1939+112A>T		intron_variant	Intron 6 of 17	2		ENSP00000420042.1
FBLN2	ENST00000477845.1	n.477+112A>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000150 AC: 12 AN: 800850 Hom.: 0 AF XY: 0.0000123 AC XY: 5 AN XY: 407292

African (AFR) AF: 0.00 AC: 0 AN: 19696

American (AMR) AF: 0.00 AC: 0 AN: 25800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16994

East Asian (EAS) AF: 0.00 AC: 0 AN: 33648

South Asian (SAS) AF: 0.00 AC: 0 AN: 57266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3158

European-Non Finnish (NFE) AF: 0.0000193 AC: 11 AN: 570554

Other (OTH) AF: 0.0000266 AC: 1 AN: 37664

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.22
PhyloP100		-5.9
Mutation Taster		=100/0	polymorphism

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: rs4596126; hg19: chr3-13659897;