rs6039

Variant names:

• chr13-113105914-G-A
• rs6039
• NM_019616.4:c.64+9G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019616.4(F7):​c.64+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,577,850 control chromosomes in the GnomAD database, including 15,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2371 hom., cov: 30)
  • Exomes 𝑓: 0.12 (13326 hom.)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.999

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-113105914-G-A is Benign according to our data. Variant chr13-113105914-G-A is described in ClinVar as [Benign]. Clinvar id is 255219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113105914-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F7	NM_019616.4	c.64+9G>A		intron_variant	Intron 1 of 7	ENST00000346342.8	NP_062562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F7	ENST00000346342.8	c.64+9G>A		intron_variant	Intron 1 of 7	1	NM_019616.4	ENSP00000329546.4
F7	ENST00000375581.3	c.64+9G>A		intron_variant	Intron 1 of 8	1		ENSP00000364731.3
F7	ENST00000541084.5	c.64+9G>A		intron_variant	Intron 1 of 5	2		ENSP00000442051.2
F7	ENST00000444337.1	n.64+9G>A		intron_variant	Intron 1 of 4	5		ENSP00000387669.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24363 AN: 151592 Hom.: 2367 Cov.: 30

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.139 AC: 27826 AN: 200172 AF XY: 0.145

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.0349

Gnomad FIN exome AF: 0.0674

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.125 AC: 177914 AN: 1426140 Hom.: 13326 Cov.: 31 AF XY: 0.130 AC XY: 91377 AN XY: 705306

Gnomad4 AFR exome AF: 0.277 AC: 9204 AN: 33194

Gnomad4 AMR exome AF: 0.123 AC: 4883 AN: 39754

Gnomad4 ASJ exome AF: 0.182 AC: 4618 AN: 25336

Gnomad4 EAS exome AF: 0.0406 AC: 1575 AN: 38758

Gnomad4 SAS exome AF: 0.273 AC: 22219 AN: 81298

Gnomad4 FIN exome AF: 0.0711 AC: 3505 AN: 49288

Gnomad4 NFE exome AF: 0.112 AC: 122365 AN: 1093738

Gnomad4 Remaining exome AF: 0.139 AC: 8229 AN: 59070

GnomAD4 genome AF: 0.161 AC: 24396 AN: 151710 Hom.: 2371 Cov.: 30 AF XY: 0.160 AC XY: 11873 AN XY: 74134

Gnomad4 AFR AF: 0.265 AC: 0.26466 AN: 0.26466

Gnomad4 AMR AF: 0.137 AC: 0.136554 AN: 0.136554

Gnomad4 ASJ AF: 0.192 AC: 0.192197 AN: 0.192197

Gnomad4 EAS AF: 0.0327 AC: 0.0326682 AN: 0.0326682

Gnomad4 SAS AF: 0.270 AC: 0.269505 AN: 0.269505

Gnomad4 FIN AF: 0.0688 AC: 0.0688481 AN: 0.0688481

Gnomad4 NFE AF: 0.117 AC: 0.116932 AN: 0.116932

Gnomad4 OTH AF: 0.174 AC: 0.17383 AN: 0.17383

Alfa AF: 0.169 Hom.: 1494

Bravo AF: 0.167

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10691850) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Factor VII deficiency Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.44
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs6039; hg19: chr13-113760228;