rs773613916

chrX-139561500-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000133.4(F9):c.839-20dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,186,263 control chromosomes in the GnomAD database, including 74 homozygotes. There are 4,325 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (0 hom., 250 hem., cov: 23)
  • Exomes 𝑓: 0.012 (74 hom. 4075 hem.)
• Consequence: F9 NM_000133.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.270

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 -10 ACMG points.

• BP6: Variant X-139561500-T-TA is Benign according to our data. Variant chrX-139561500-T-TA is described in ClinVar as [Benign]. Clinvar id is 255227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00785 (882/112371) while in subpopulation NFE AF= 0.0123 (654/53289). AF 95% confidence interval is 0.0115. There are 0 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 250 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F9	NM_000133.4	c.839-20dup		intron_variant		ENST00000218099.7
F9	NM_001313913.2	c.725-20dup		intron_variant
F9	XM_005262397.5	c.710-20dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F9	ENST00000218099.7	c.839-20dup		intron_variant		1	NM_000133.4	P1
F9	ENST00000394090.2	c.725-20dup		intron_variant		1
F9	ENST00000643157.1	n.1506-20dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00786 AC: 883 AN: 112313 Hom.: 0 Cov.: 23 AF XY: 0.00725 AC XY: 250 AN XY: 34473

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.0117

Gnomad AMR AF: 0.00755

Gnomad ASJ AF: 0.00754

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00260

Gnomad FIN AF: 0.00736

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00891 AC: 1545 AN: 173494 Hom.: 10 AF XY: 0.00918 AC XY: 547 AN XY: 59618

Gnomad AFR exome AF: 0.000543

Gnomad AMR exome AF: 0.00832

Gnomad ASJ exome AF: 0.00500

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00266

Gnomad FIN exome AF: 0.00954

Gnomad NFE exome AF: 0.0134

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.0124 AC: 13297 AN: 1073892 Hom.: 74 Cov.: 26 AF XY: 0.0119 AC XY: 4075 AN XY: 342576

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.00835

Gnomad4 ASJ exome AF: 0.00612

Gnomad4 EAS exome AF: 0.0000333

Gnomad4 SAS exome AF: 0.00316

Gnomad4 FIN exome AF: 0.00930

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.00785 AC: 882 AN: 112371 Hom.: 0 Cov.: 23 AF XY: 0.00724 AC XY: 250 AN XY: 34541

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.00754

Gnomad4 ASJ AF: 0.00754

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00261

Gnomad4 FIN AF: 0.00736

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00800 Hom.: 60

Bravo AF: 0.00797

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
La Branchor		0.69

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: rs773613916; hg19: chrX-138643659;