chr13-113109612-G-T

Variant names:

• chr13-113109612-G-T
• rs1475931
• NM_019616.4:c.65-1078G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019616.4(F7):​c.65-1078G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,016 control chromosomes in the GnomAD database, including 6,920 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 0.29 (6920 hom., cov: 33)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 14 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), Laboratory for Molecular Medicine, Orphanet, Ambry Genetics
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F7	NM_019616.4	MANE Select	c.65-1078G>T		intron	N/A	NP_062562.1
	F7	NM_000131.5		c.131-1078G>T		intron	N/A	NP_000122.1
	F7	NM_001267554.2		c.64+3707G>T		intron	N/A	NP_001254483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F7	ENST00000346342.8	TSL:1 MANE Select	c.65-1078G>T		intron	N/A	ENSP00000329546.4
	F7	ENST00000375581.3	TSL:1	c.131-1078G>T		intron	N/A	ENSP00000364731.3
	F7	ENST00000541084.5	TSL:2	c.64+3707G>T		intron	N/A	ENSP00000442051.2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44193 AN: 151898 Hom.: 6897 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.291 AC: 44249 AN: 152016 Hom.: 6920 Cov.: 33 AF XY: 0.292 AC XY: 21677 AN XY: 74280

African (AFR) AF: 0.389 AC: 16108 AN: 41462

American (AMR) AF: 0.359 AC: 5493 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1049 AN: 3464

East Asian (EAS) AF: 0.438 AC: 2247 AN: 5132

South Asian (SAS) AF: 0.203 AC: 981 AN: 4830

European-Finnish (FIN) AF: 0.236 AC: 2497 AN: 10576

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15013 AN: 67946

Other (OTH) AF: 0.295 AC: 621 AN: 2106

Alfa AF: 0.238 Hom.: 7104

Bravo AF: 0.306

Asia WGS AF: 0.328 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.97
PhyloP100		-0.59
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: rs1475931; hg19: chr13-113763926;