rs488703

Variant names:

• chr13-113116562-G-A
• rs488703
• NM_019616.4:c.506-204G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-113116562-G-A
• chr13-113116562-G-C
• chr13-113116562-G-T

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.506-204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,216 control chromosomes in the GnomAD database, including 1,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1688 hom., cov: 33)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0810
• Publications: 29 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-113116562-G-A is Benign according to our data. Variant chr13-113116562-G-A is described in ClinVar as Benign. ClinVar VariationId is 1291650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 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.506-204G>A		intron	N/A	NP_062562.1	P08709-2
	F7	NM_000131.5		c.572-204G>A		intron	N/A	NP_000122.1
	F7	NM_001267554.2		c.320-204G>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.506-204G>A		intron	N/A	ENSP00000329546.4	P08709-2
	F7	ENST00000375581.3	TSL:1	c.572-204G>A		intron	N/A	ENSP00000364731.3	P08709-1
	F7	ENST00000891255.1		c.719-204G>A		intron	N/A	ENSP00000561314.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20868 AN: 152098 Hom.: 1675 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.137 AC: 20910 AN: 152216 Hom.: 1688 Cov.: 33 AF XY: 0.137 AC XY: 10230 AN XY: 74428

African (AFR) AF: 0.193 AC: 8002 AN: 41528

American (AMR) AF: 0.124 AC: 1893 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3472

East Asian (EAS) AF: 0.0468 AC: 242 AN: 5174

South Asian (SAS) AF: 0.271 AC: 1308 AN: 4818

European-Finnish (FIN) AF: 0.0697 AC: 739 AN: 10610

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7480 AN: 68010

Other (OTH) AF: 0.151 AC: 319 AN: 2112

Alfa AF: 0.127 Hom.: 1042

Bravo AF: 0.141

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	2.5
DANN	Benign	0.68
PhyloP100		0.081
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: rs488703; hg19: chr13-113770876;