rs74693003

Variant names:

• chr9-134880404-G-A
• rs74693003
• XM_011518392.4:c.68-2122G>A

Variant summary

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

The XM_011518392.4(FCN2):​c.68-2122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 152,334 control chromosomes in the GnomAD database, including 2 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 0.00098 (2 hom., cov: 33)
• Consequence: FCN2 XM_011518392.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.992
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	XM_011518392.4	c.68-2122G>A		intron_variant	Intron 1 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.68-2898G>A		intron_variant	Intron 1 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.000979 AC: 149 AN: 152216 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.000957

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

GnomAD4 genome AF: 0.000978 AC: 149 AN: 152334 Hom.: 2 Cov.: 33 AF XY: 0.00118 AC XY: 88 AN XY: 74488

African (AFR) AF: 0.000168 AC: 7 AN: 41584

American (AMR) AF: 0.000392 AC: 6 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00112 AC: 76 AN: 68028

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000763 Hom.: 0

Bravo AF: 0.000699

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.9
DANN	Benign	0.47
PhyloP100		0.99
PromoterAI		-0.0090	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs74693003; hg19: chr9-137772250;