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
• Publications: 16 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, Laboratory for Molecular Medicine
• factor VII deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

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 VariationId is 255219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

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.64+9G>A		intron	N/A	NP_062562.1	P08709-2
	F7	NM_000131.5		c.64+9G>A		intron	N/A	NP_000122.1
	F7	NM_001267554.2		c.64+9G>A		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.64+9G>A		intron	N/A	ENSP00000329546.4	P08709-2
	F7	ENST00000375581.3	TSL:1	c.64+9G>A		intron	N/A	ENSP00000364731.3	P08709-1
	F7	ENST00000891255.1		c.64+9G>A		intron	N/A	ENSP00000561314.1

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

African (AFR) AF: 0.277 AC: 9204 AN: 33194

American (AMR) AF: 0.123 AC: 4883 AN: 39754

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4618 AN: 25336

East Asian (EAS) AF: 0.0406 AC: 1575 AN: 38758

South Asian (SAS) AF: 0.273 AC: 22219 AN: 81298

European-Finnish (FIN) AF: 0.0711 AC: 3505 AN: 49288

Middle Eastern (MID) AF: 0.231 AC: 1316 AN: 5704

European-Non Finnish (NFE) AF: 0.112 AC: 122365 AN: 1093738

Other (OTH) 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

African (AFR) AF: 0.265 AC: 10931 AN: 41302

American (AMR) AF: 0.137 AC: 2086 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3460

East Asian (EAS) AF: 0.0327 AC: 167 AN: 5112

South Asian (SAS) AF: 0.270 AC: 1285 AN: 4768

European-Finnish (FIN) AF: 0.0688 AC: 728 AN: 10574

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7942 AN: 67920

Other (OTH) AF: 0.174 AC: 364 AN: 2094

Alfa AF: 0.169 Hom.: 1494

Bravo AF: 0.167

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Factor VII deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		-1.0
PromoterAI		-0.023	Neutral
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

Other links and lift over

dbSNP: rs6039; hg19: chr13-113760228;