rs422187

Positions:

• chrX-139550700-A-C
• chrX-139550700-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000133.4(F9):​c.521-362A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 110,725 control chromosomes in the GnomAD database, including 5,837 homozygotes. There are 10,784 hemizygotes in GnomAD. 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 0.35 (5837 hom., 10784 hem., cov: 22)
• Consequence: F9 NM_000133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

Genes affected

F9 (HGNC:3551): (coagulation factor IX) This gene encodes vitamin K-dependent coagulation factor IX that circulates in the blood as an inactive zymogen. This factor is converted to an active form by factor XIa, which excises the activation peptide and thus generates a heavy chain and a light chain held together by one or more disulfide bonds. The role of this activated factor IX in the blood coagulation cascade is to activate factor X to its active form through interactions with Ca+2 ions, membrane phospholipids, and factor VIII. Alterations of this gene, including point mutations, insertions and deletions, cause factor IX deficiency, which is a recessive X-linked disorder, also called hemophilia B or Christmas disease. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Sep 2015]

F9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F9	NM_000133.4	c.521-362A>C		intron_variant		ENST00000218099.7	NP_000124.1
F9	NM_001313913.2	c.407-362A>C		intron_variant			NP_001300842.1
F9	XM_005262397.5	c.392-362A>C		intron_variant			XP_005262454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F9	ENST00000218099.7	c.521-362A>C		intron_variant		1	NM_000133.4	ENSP00000218099.2
F9	ENST00000394090.2	c.407-362A>C		intron_variant		1		ENSP00000377650.2
F9	ENST00000643157.1	n.1188-362A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.348 AC: 38544 AN: 110672 Hom.: 5840 Cov.: 22 AF XY: 0.326 AC XY: 10744 AN XY: 32948

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00420

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.348 AC: 38582 AN: 110725 Hom.: 5837 Cov.: 22 AF XY: 0.327 AC XY: 10784 AN XY: 33011

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.00450

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.276

Alfa AF: 0.276 Hom.: 5557

Bravo AF: 0.352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.6
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs422187; hg19: chrX-138632859;