rs6039

Variant names:

• chr13-113105914-G-A
• rs6039
• NM_019616.4:c.64+9G>A

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_019616.4(F7):c.64+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene F7 is a cancer driver gene (CancerMine: 1 driver citations). The variant allele was found at a cumulative frequency of 0.128 (AC=202,310) in the gnomAD database across 1,577,850 control chromosomes, including 15,697 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.273. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely 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:6
• Conservation: PhyloP100: -0.999
• Publications: 2 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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet
• factor VII deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.273 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_019616.4. You can select a different transcript below to see updated classification 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	Intron 1 of 7	Prot: NP_062562.1 UniProt:
	F7 NM_000131.5		c.64+9G>A	intron	Intron 1 of 8	Prot: NP_000122.1 UniProt:
	F7 NM_001267554.2		c.64+9G>A	intron	Intron 1 of 5	Prot: NP_001254483.1 UniProt:

F7 NM_019616.4

MANE Select

HGVSc / HGVSpc.64+9G>A

Exon rankIntron 1 of 7

intron

Prot: NP_062562.1UniProt: P08709-2

F7 NM_000131.5

HGVSc / HGVSpc.64+9G>A

Exon rankIntron 1 of 8

intron

Prot: NP_000122.1UniProt: P08709-1

F7 NM_001267554.2

HGVSc / HGVSpc.64+9G>A

Exon rankIntron 1 of 5

intron

Prot: NP_001254483.1UniProt: F5H8B0

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	F7 ENST00000346342.8	TSL:1MANE Select	c.64+9G>A	intron	Intron 1 of 7	Prot: ENSP00000329546.4 UniProt:
	F7 ENST00000375581.3	TSL:1	c.64+9G>A	intron	Intron 1 of 8	Prot: ENSP00000364731.3 UniProt:
	F7 ENST00000891255.1		c.64+9G>A	intron	Intron 1 of 8	Prot: ENSP00000561314.1 UniProt:

F7 ENST00000346342.8

TSL:1MANE Select

HGVSc / HGVSpc.64+9G>A

Exon rankIntron 1 of 7

intron

Prot: ENSP00000329546.4UniProt: P08709-2

F7 ENST00000375581.3

TSL:1

HGVSc / HGVSpc.64+9G>A

Exon rankIntron 1 of 8

intron

Prot: ENSP00000364731.3UniProt: P08709-1

F7 ENST00000891255.1

HGVSc / HGVSpc.64+9G>A

Exon rankIntron 1 of 8

intron

Prot: ENSP00000561314.1UniProt: A0ACI8QDK7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.161	AC:24363	Hom:2367	AN:151592	Cov:30
GnomAD2 exomes	AF: 0.139	AC:27826	Hom:	AN:200172	Cov:
GnomAD4 exome	AF: 0.125	AC:177914	Hom:13326	AN:1426140	Cov:31
GnomAD4 genome	AF: 0.161	AC:24396	Hom:2371	AN:151710	Cov:30
TOPMed (Bravo)	AF: 0.167	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.172	AC:18067	Hom:1827	AN:105292	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.184	AC:430	Hom:48	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0380	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.0933	AC:28	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.163	AC:2105	Hom:	AN:12928	Cov:
GenomeAsia100K	AF: 0.158	AC:549	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.0300	AC:216	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.199	AC:35	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0427	AC:5226	Hom:143	AN:122298	Cov:
Turkish Variome	AF: 0.198	AC:1301	Hom:137	AN:6558	Cov:
UK10K	AF: 0.116	AC:880	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0387	AC:347	Hom:9	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
BipEx(Bipolar disorder (including schizoaffective))	0.114	3213	28278	0.114	3291	28780
SCHEMA(Schizophrenia)	0.178	21673	121586	0.184	38110	206742

Showing 2 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Factor VII deficiency (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.2
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.44
GPN-Star LLR	N/A	-1.3
GPN-Star score	N/A	1.3
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-1.0
PromoterAI	N/A	-0.023	Neutral
RBP_binding_hub_radar	N/A	0.85
RBP_regulation_power_radar	N/A	2.0

Showing 11 of 11 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.020
SpliceAI score (max)	Benign	0.030	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs6039;

hg19: chr13-113760228;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar