rs4898399

chrX-154859093-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000132.4(F8):c.6900+1339A>T 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 0.82 (26269 hom., 26368 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: F8 NM_000132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS2: High Homozygotes in GnomAd at 26279 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F8	NM_000132.4	c.6900+1339A>T		intron_variant		ENST00000360256.9
F8	NM_019863.3	c.495+1339A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F8	ENST00000360256.9	c.6900+1339A>T		intron_variant		1	NM_000132.4	P1
F8	ENST00000330287.10	c.495+1339A>T		intron_variant		1
F8	ENST00000644698.1	c.633+1339A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.823 AC: 90094 AN: 109432 Hom.: 26279 Cov.: 21 AF XY: 0.831 AC XY: 26318 AN XY: 31668

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.916

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.850

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: 0.823 AC: 90127 AN: 109486 Hom.: 26269 Cov.: 21 AF XY: 0.831 AC XY: 26368 AN XY: 31732

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.854

Alfa AF: 0.823 Hom.: 7014

Bravo AF: 0.820

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.4
Dann	Benign	0.65

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: rs4898399; hg19: chrX-154087368;