chr13-113105720-T-G

Variant names:

• chr13-113105720-T-G
• rs561241
• NM_019616.4:c.-122T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019616.4(F7):​c.-122T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: F7 NM_019616.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 48 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

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.-122T>G		upstream_gene	N/A	NP_062562.1
	F7	NM_000131.5		c.-122T>G		upstream_gene	N/A	NP_000122.1
	F7	NM_001267554.2		c.-122T>G		upstream_gene	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.-122T>G		upstream_gene	N/A	ENSP00000329546.4
	F7	ENST00000375581.3	TSL:1	c.-122T>G		upstream_gene	N/A	ENSP00000364731.3
	F7	ENST00000541084.5	TSL:2	c.-122T>G		upstream_gene	N/A	ENSP00000442051.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 994352 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 503394

African (AFR) AF: 0.00 AC: 0 AN: 23896

American (AMR) AF: 0.00 AC: 0 AN: 35068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22742

East Asian (EAS) AF: 0.00 AC: 0 AN: 33666

South Asian (SAS) AF: 0.00 AC: 0 AN: 71144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4828

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 722680

Other (OTH) AF: 0.00 AC: 0 AN: 44776

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.4
DANN	Benign	0.87
PhyloP100		-1.1
PromoterAI		-0.0094	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs561241; hg19: chr13-113760034;