rs4149754

Positions:

• chrX-139531533-G-A

Variant summary

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

The NM_000133.4(F9):​c.88+681G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 111,988 control chromosomes in the GnomAD database, including 147 homozygotes. There are 1,738 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 0.053 (147 hom., 1738 hem., cov: 23)
• Consequence: F9 NM_000133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F9	NM_000133.4	c.88+681G>A		intron_variant		ENST00000218099.7	NP_000124.1
F9	NM_001313913.2	c.88+681G>A		intron_variant			NP_001300842.1
F9	XM_005262397.5	c.88+681G>A		intron_variant			XP_005262454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F9	ENST00000218099.7	c.88+681G>A		intron_variant		1	NM_000133.4	ENSP00000218099.2
F9	ENST00000394090.2	c.88+681G>A		intron_variant		1		ENSP00000377650.2
F9	ENST00000479617.2	n.95+681G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 5892 AN: 111937 Hom.: 148 Cov.: 23 AF XY: 0.0509 AC XY: 1736 AN XY: 34123

Gnomad AFR AF: 0.00994

Gnomad AMI AF: 0.0586

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00112

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.0475

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

GnomAD4 genome AF: 0.0526 AC: 5886 AN: 111988 Hom.: 147 Cov.: 23 AF XY: 0.0508 AC XY: 1738 AN XY: 34184

Gnomad4 AFR AF: 0.00992

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.0672

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.0463

Alfa AF: 0.0738 Hom.: 1152

Bravo AF: 0.0483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs4149754; hg19: chrX-138613692;