rs4596126

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-13618397-A-C
• chr3-13618397-A-T

Variant summary

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

The NM_001004019.2(FBLN2):​c.1939+112A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 951,736 control chromosomes in the GnomAD database, including 44,859 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 0.39 (17009 hom., cov: 33)
  • Exomes 𝑓: 0.24 (27850 hom.)
• Consequence: FBLN2 NM_001004019.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.93
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBLN2	NM_001004019.2	c.1939+112A>C		intron_variant	Intron 6 of 17	ENST00000404922.8	NP_001004019.1
SNORA93	NR_132775.1	n.17A>C		non_coding_transcript_exon_variant	Exon 1 of 1
FBLN2	NM_001165035.2	c.1939+112A>C		intron_variant	Intron 6 of 17		NP_001158507.1
FBLN2	NM_001998.3	c.1939+112A>C		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>C		intron_variant	Intron 6 of 17	5	NM_001004019.2	ENSP00000384169.3
FBLN2	ENST00000295760.11	c.1939+112A>C		intron_variant	Intron 6 of 16	1		ENSP00000295760.7
FBLN2	ENST00000492059.5	c.1939+112A>C		intron_variant	Intron 6 of 17	2		ENSP00000420042.1
FBLN2	ENST00000477845.1	n.477+112A>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59612 AN: 152092 Hom.: 16957 Cov.: 33

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.243 AC: 193914 AN: 799526 Hom.: 27850 AF XY: 0.242 AC XY: 98268 AN XY: 406698

African (AFR) AF: 0.828 AC: 16290 AN: 19684

American (AMR) AF: 0.181 AC: 4657 AN: 25788

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 4087 AN: 16982

East Asian (EAS) AF: 0.147 AC: 4932 AN: 33644

South Asian (SAS) AF: 0.258 AC: 14762 AN: 57232

European-Finnish (FIN) AF: 0.240 AC: 8645 AN: 36038

Middle Eastern (MID) AF: 0.247 AC: 778 AN: 3156

European-Non Finnish (NFE) AF: 0.227 AC: 129523 AN: 569378

Other (OTH) AF: 0.272 AC: 10240 AN: 37624

GnomAD4 genome AF: 0.392 AC: 59724 AN: 152210 Hom.: 17009 Cov.: 33 AF XY: 0.388 AC XY: 28843 AN XY: 74432

African (AFR) AF: 0.813 AC: 33776 AN: 41544

American (AMR) AF: 0.230 AC: 3515 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.185 AC: 956 AN: 5168

South Asian (SAS) AF: 0.266 AC: 1282 AN: 4824

European-Finnish (FIN) AF: 0.239 AC: 2535 AN: 10602

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15892 AN: 67978

Other (OTH) AF: 0.347 AC: 734 AN: 2116

Alfa AF: 0.284 Hom.: 22251

Bravo AF: 0.411

Asia WGS AF: 0.303 AC: 1052 AN: 3478

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	0.51
PhyloP100		-5.9
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: rs4596126; hg19: chr3-13659897;