rs11103563

Variant names:

• chr9-134886852-A-G
• rs11103563
• NM_004108.3:c.694+288A>G

Variant summary

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

The NM_004108.3(FCN2):​c.694+288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,142 control chromosomes in the GnomAD database, including 1,465 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 0.14 (1465 hom., cov: 32)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 8 publications found

Genes affected

FCN2 (HGNC:3624): (ficolin 2) The product of this gene belongs to the ficolin family of proteins. This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. This gene is predominantly expressed in the liver, and has been shown to have carbohydrate binding and opsonic activities. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.694+288A>G		intron_variant	Intron 7 of 7	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.580+288A>G		intron_variant	Intron 6 of 6		NP_056652.1
FCN2	XM_011518392.4	c.661+288A>G		intron_variant	Intron 7 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.547+288A>G		intron_variant	Intron 6 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.694+288A>G		intron_variant	Intron 7 of 7	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.580+288A>G		intron_variant	Intron 6 of 6	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20568 AN: 152024 Hom.: 1465 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0419

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20592 AN: 152142 Hom.: 1465 Cov.: 32 AF XY: 0.134 AC XY: 9930 AN XY: 74376

African (AFR) AF: 0.196 AC: 8126 AN: 41488

American (AMR) AF: 0.125 AC: 1915 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0419 AC: 145 AN: 3464

East Asian (EAS) AF: 0.181 AC: 935 AN: 5166

South Asian (SAS) AF: 0.122 AC: 586 AN: 4822

European-Finnish (FIN) AF: 0.0944 AC: 1001 AN: 10600

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7574 AN: 67992

Other (OTH) AF: 0.133 AC: 280 AN: 2112

Alfa AF: 0.134 Hom.: 191

Bravo AF: 0.141

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.23
DANN	Benign	0.56
PhyloP100		-1.5
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: rs11103563; hg19: chr9-137778698;