chr13-113114912-A-C

Variant names:

• chr13-113114912-A-C
• rs3093265
• NM_019616.4:c.365-748A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

F7 Gene-Disease associations (from GenCC):

• congenital factor VII deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• factor VII deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 86 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019616.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F7	NM_019616.4	MANE Select	c.365-748A>C		intron	N/A	NP_062562.1	P08709-2
	F7	NM_000131.5		c.431-748A>C		intron	N/A	NP_000122.1
	F7	NM_001267554.2		c.179-748A>C		intron	N/A	NP_001254483.1	F5H8B0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F7	ENST00000346342.8	TSL:1 MANE Select	c.365-748A>C		intron	N/A	ENSP00000329546.4	P08709-2
	F7	ENST00000375581.3	TSL:1	c.431-748A>C		intron	N/A	ENSP00000364731.3	P08709-1
	F7	ENST00000891255.1		c.470-48A>C		intron	N/A	ENSP00000561314.1

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

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 40

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0337 AC: 36 AN: 1068

Other (OTH) AF: 0.0217 AC: 1 AN: 46

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

African (AFR) AF: 0.0199 AC: 827 AN: 41568

American (AMR) AF: 0.0249 AC: 381 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3472

East Asian (EAS) AF: 0.0181 AC: 94 AN: 5182

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4826

European-Finnish (FIN) AF: 0.0367 AC: 390 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0438 AC: 2977 AN: 68032

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0403 Hom.: 199

Bravo AF: 0.0306

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3093265; hg19: chr13-113769226;