rs438601

Positions:

• chrX-139537760-C-G

Variant summary

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

The NM_000133.4(F9):​c.277+374C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 110,829 control chromosomes in the GnomAD database, including 1,267 homozygotes. There are 4,940 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 0.16 (1267 hom., 4940 hem., cov: 22)
• Consequence: F9 NM_000133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F9	NM_000133.4	c.277+374C>G		intron_variant		ENST00000218099.7	NP_000124.1
F9	NM_001313913.2	c.277+374C>G		intron_variant			NP_001300842.1
F9	XM_005262397.5	c.277+374C>G		intron_variant			XP_005262454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F9	ENST00000218099.7	c.277+374C>G		intron_variant		1	NM_000133.4	ENSP00000218099.2
F9	ENST00000394090.2	c.277+374C>G		intron_variant		1		ENSP00000377650.2
F9	ENST00000479617.2	n.241+605C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 17522 AN: 110778 Hom.: 1270 Cov.: 22 AF XY: 0.150 AC XY: 4937 AN XY: 32992

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.00369

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.251

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.158 AC: 17514 AN: 110829 Hom.: 1267 Cov.: 22 AF XY: 0.149 AC XY: 4940 AN XY: 33055

Gnomad4 AFR AF: 0.0726

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.00398

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.141

Alfa AF: 0.190 Hom.: 1283

Bravo AF: 0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.41

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: rs438601; hg19: chrX-138619919;