rs3128626

Variant names:

• chr9-134881710-G-A
• rs3128626
• NM_004108.3:c.100+789G>A

Variant summary

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

The NM_004108.3(FCN2):​c.100+789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,146 control chromosomes in the GnomAD database, including 4,543 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 0.22 (4543 hom., cov: 32)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.100+789G>A		intron_variant	Intron 1 of 7	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.100+789G>A		intron_variant	Intron 1 of 6		NP_056652.1
FCN2	XM_011518392.4	c.68-816G>A		intron_variant	Intron 1 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.68-1592G>A		intron_variant	Intron 1 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.100+789G>A		intron_variant	Intron 1 of 7	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.100+789G>A		intron_variant	Intron 1 of 6	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33950 AN: 152028 Hom.: 4537 Cov.: 32

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.223 AC: 33949 AN: 152146 Hom.: 4543 Cov.: 32 AF XY: 0.224 AC XY: 16639 AN XY: 74370

African (AFR) AF: 0.0680 AC: 2823 AN: 41524

American (AMR) AF: 0.236 AC: 3605 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1696 AN: 5146

South Asian (SAS) AF: 0.382 AC: 1844 AN: 4822

European-Finnish (FIN) AF: 0.265 AC: 2811 AN: 10588

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19285 AN: 67988

Other (OTH) AF: 0.256 AC: 542 AN: 2114

Alfa AF: 0.266 Hom.: 6994

Bravo AF: 0.213

Asia WGS AF: 0.341 AC: 1183 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	2.0
DANN	Benign	0.52
PhyloP100		-0.53
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: rs3128626; hg19: chr9-137773556;