13-113106101-G-A

Variant names:

• chr13-113106101-G-A
• rs2774030
• NM_019616.4:c.64+196G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019616.4(F7):​c.64+196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 149,540 control chromosomes in the GnomAD database, including 26,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.59 (26587 hom., cov: 23)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.789
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-113106101-G-A is Benign according to our data. Variant chr13-113106101-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 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+196G>A		intron	N/A	NP_062562.1	P08709-2
	F7	NM_000131.5		c.64+196G>A		intron	N/A	NP_000122.1
	F7	NM_001267554.2		c.64+196G>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+196G>A		intron	N/A	ENSP00000329546.4	P08709-2
	F7	ENST00000375581.3	TSL:1	c.64+196G>A		intron	N/A	ENSP00000364731.3	P08709-1
	F7	ENST00000891255.1		c.64+196G>A		intron	N/A	ENSP00000561314.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 88643 AN: 149420 Hom.: 26573 Cov.: 23

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.612

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.593 AC: 88689 AN: 149540 Hom.: 26587 Cov.: 23 AF XY: 0.590 AC XY: 42997 AN XY: 72834

African (AFR) AF: 0.507 AC: 20525 AN: 40490

American (AMR) AF: 0.590 AC: 8895 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2536 AN: 3464

East Asian (EAS) AF: 0.508 AC: 2446 AN: 4816

South Asian (SAS) AF: 0.583 AC: 2709 AN: 4648

European-Finnish (FIN) AF: 0.600 AC: 6162 AN: 10274

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43455 AN: 67528

Other (OTH) AF: 0.617 AC: 1273 AN: 2064

Alfa AF: 0.611 Hom.: 6530

Bravo AF: 0.584

Asia WGS AF: 0.534 AC: 1860 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.44
PhyloP100		-0.79
PromoterAI		-0.0017	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)		0.0		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: rs2774030; hg19: chr13-113760415;