rs3093265

chr13-113114912-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_019616.4(F7):c.365-748A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 153,642 control chromosomes in the GnomAD database, including 86 homozygotes. 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 0.033 (86 hom., cov: 33)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

Genes affected

F7 (HGNC:3544): (coagulation factor VII) This gene encodes coagulation factor VII which is a vitamin K-dependent factor essential for hemostasis. This factor circulates in the blood in a zymogen form, and is converted to an active form by either factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of the factor VII, a heavy chain containing a catalytic domain and a light chain containing 2 EGF-like domains are generated, and two chains are held together by a disulfide bond. In the presence of factor III and calcium ions, the activated factor then further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Defects in this gene can cause coagulopathy. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0325 (4957/152320) while in subpopulation NFE AF= 0.0438 (2977/68032). AF 95% confidence interval is 0.0424. There are 86 homozygotes in gnomad4. There are 2441 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 86 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F7	NM_019616.4	c.365-748A>C		intron_variant		ENST00000346342.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F7	ENST00000346342.8	c.365-748A>C		intron_variant		1	NM_019616.4	P2

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4946 AN: 152202 Hom.: 86 Cov.: 33

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.00994

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.0287 AC: 38 AN: 1322 Hom.: 0 Cov.: 0 AF XY: 0.0293 AC XY: 20 AN XY: 682

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.0337

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0325 AC: 4957 AN: 152320 Hom.: 86 Cov.: 33 AF XY: 0.0328 AC XY: 2441 AN XY: 74480

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.0249

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.0102

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0363 Hom.: 19

Bravo AF: 0.0306

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.8
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3093265; hg19: chr13-113769226;