Variant rs773613916 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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 (★). There are indicators that this mutation may affect the branch point..

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.270

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 250 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
F9	NM_000133.4 linkuse as main transcript	c.839-20dup	intron_variant	ENST00000218099.7	NP_000124.1
F9	NM_001313913.2 linkuse as main transcript	c.725-20dup	intron_variant		NP_001300842.1
F9	XM_005262397.5 linkuse as main transcript	c.710-20dup	intron_variant		XP_005262454.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
F9	ENST00000218099.7 linkuse as main transcript	c.839-20dup	intron_variant	1	NM_000133.4	ENSP00000218099	P1	P00740-1
F9	ENST00000394090.2 linkuse as main transcript	c.725-20dup	intron_variant	1		ENSP00000377650		P00740-2
F9	ENST00000643157.1 linkuse as main transcript	n.1506-20dup	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00786

AC:

883

AN:

112313

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

250

AN XY:

34473

show subpopulations

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.:

AF XY:

0.00918

AC XY:

547

AN XY:

59618

show subpopulations

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.:

Cov.:

AF XY:

0.0119

AC XY:

4075

AN XY:

342576

show subpopulations

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.:

Cov.:

AF XY:

0.00724

AC XY:

250

AN XY:

34541

show subpopulations

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.:

Bravo

AF:

0.00797

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

4.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over