Variant chrX-154903815-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000132.4(F8):c.5998+91T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 775,751 control chromosomes in the GnomAD database, including 33,605 homozygotes. There are 71,495 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 9839 hom., 13681 hem., cov: 23)

Exomes 𝑓: 0.30 ( 23766 hom. 57814 hem. )

Consequence

F8
NM_000132.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.384

Variant links:

Genes affected

F8 (HGNC:3546): (coagulation factor VIII) This gene encodes coagulation factor VIII, which participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder. [provided by RefSeq, Jul 2008]

F8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant X-154903815-A-T is Benign according to our data. Variant chrX-154903815-A-T is described in ClinVar as [Benign]. Clinvar id is 1251259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F8	NM_000132.4 linkuse as main transcript	c.5998+91T>A		intron_variant		ENST00000360256.9	NP_000123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F8	ENST00000360256.9 linkuse as main transcript	c.5998+91T>A		intron_variant		1	NM_000132.4	ENSP00000353393	P1	P00451-1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

47554

AN:

111046

Hom.:

9838

Cov.:

AF XY:

0.410

AC XY:

13635

AN XY:

33240

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.412

GnomAD4 exome

AF:

0.299

AC:

198409

AN:

664652

Hom.:

23766

AF XY:

0.308

AC XY:

57814

AN XY:

187544

show subpopulations

Gnomad4 AFR exome

AF:

0.823

Gnomad4 AMR exome

AF:

0.441

Gnomad4 ASJ exome

AF:

0.320

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.397

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.323

GnomAD4 genome

AF:

0.428

AC:

47598

AN:

111099

Hom.:

9839

Cov.:

AF XY:

0.411

AC XY:

13681

AN XY:

33303

show subpopulations

Gnomad4 AFR

AF:

0.816

Gnomad4 AMR

AF:

0.388

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.364

Hom.:

2849

Bravo

AF:

0.456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.68

DANN

Benign

0.76

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