rs73565973

Variant names:

• chr9-134882872-T-C
• rs73565973
• NM_004108.3:c.214+233T>C

Variant summary

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

The NM_004108.3(FCN2):​c.214+233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,172 control chromosomes in the GnomAD database, including 1,489 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 0.13 (1489 hom., cov: 33)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 5 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=-0.91).
• 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.214+233T>C		intron_variant	Intron 2 of 7	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.101-430T>C		intron_variant	Intron 1 of 6		NP_056652.1
FCN2	XM_011518392.4	c.181+233T>C		intron_variant	Intron 2 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.68-430T>C		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.214+233T>C		intron_variant	Intron 2 of 7	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.101-430T>C		intron_variant	Intron 1 of 6	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20433 AN: 152054 Hom.: 1487 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.134 AC: 20457 AN: 152172 Hom.: 1489 Cov.: 33 AF XY: 0.132 AC XY: 9846 AN XY: 74406

African (AFR) AF: 0.196 AC: 8135 AN: 41516

American (AMR) AF: 0.120 AC: 1833 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.180 AC: 930 AN: 5168

South Asian (SAS) AF: 0.121 AC: 584 AN: 4826

European-Finnish (FIN) AF: 0.0943 AC: 1000 AN: 10606

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

European-Non Finnish (NFE) AF: 0.111 AC: 7528 AN: 67980

Other (OTH) AF: 0.129 AC: 273 AN: 2112

Alfa AF: 0.135 Hom.: 200

Bravo AF: 0.140

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs73565973; hg19: chr9-137774718;