X-139532512-T-C

Position:

• chrX-139532512-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000133.4(F9):​c.88+1660T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.65 (16829 hom., 20966 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: F9 NM_000133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F9	NM_000133.4	c.88+1660T>C		intron_variant		ENST00000218099.7
F9	NM_001313913.2	c.88+1660T>C		intron_variant
F9	XM_005262397.5	c.88+1660T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F9	ENST00000218099.7	c.88+1660T>C		intron_variant		1	NM_000133.4	P1
F9	ENST00000394090.2	c.88+1660T>C		intron_variant		1
F9	ENST00000479617.2	n.95+1660T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.646 AC: 71133 AN: 110075 Hom.: 16827 Cov.: 23 AF XY: 0.647 AC XY: 20936 AN XY: 32345

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.660

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.697

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.646 AC: 71170 AN: 110129 Hom.: 16829 Cov.: 23 AF XY: 0.647 AC XY: 20966 AN XY: 32409

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.700

Alfa AF: 0.603 Hom.: 5531

Bravo AF: 0.651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.023
DANN	Benign	0.47

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: rs401597; hg19: chrX-138614671;