rs1801020

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000505.4(F12):c.-4T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,613,300 control chromosomes in the GnomAD database, including 413,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 34772 hom., cov: 31)

Exomes 𝑓: 0.71 ( 378507 hom. )

Consequence

F12
NM_000505.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.57

Publications

172 publications found

Variant links:

Genes affected

F12 (HGNC:3530): (coagulation factor XII) This gene encodes coagulation factor XII which circulates in blood as a zymogen. This single chain zymogen is converted to a two-chain serine protease with an heavy chain (alpha-factor XIIa) and a light chain. The heavy chain contains two fibronectin-type domains, two epidermal growth factor (EGF)-like domains, a kringle domain and a proline-rich domain, whereas the light chain contains only a catalytic domain. On activation, further cleavages takes place in the heavy chain, resulting in the production of beta-factor XIIa light chain and the alpha-factor XIIa light chain becomes beta-factor XIIa heavy chain. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then to beta-factor XIIa. The active factor XIIa participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. It activates coagulation factors VII and XI. Defects in this gene do not cause any clinical symptoms and the sole effect is that whole-blood clotting time is prolonged. [provided by RefSeq, Jul 2008]

F12 links:

GRK6 (HGNC:4545): (G protein-coupled receptor kinase 6) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

GRK6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 5-177409531-A-G is Benign according to our data. Variant chr5-177409531-A-G is described in ClinVar as Benign. ClinVar VariationId is 1167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000505.4. 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
	F12	NM_000505.4	MANE Select	c.-4T>C		5_prime_UTR	Exon 1 of 14	NP_000496.2	P00748

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F12	ENST00000253496.4	TSL:1 MANE Select	c.-4T>C	5_prime_UTR	Exon 1 of 14	ENSP00000253496.3	P00748
F12	ENST00000898128.1		c.-4T>C	5_prime_UTR	Exon 1 of 15	ENSP00000568187.1
F12	ENST00000898127.1		c.-4T>C	5_prime_UTR	Exon 1 of 13	ENSP00000568186.1

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

100982

AN:

151938

Hom.:

34763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.552

Gnomad AMI

AF:

0.874

Gnomad AMR

AF:

0.665

Gnomad ASJ

AF:

0.816

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.740

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.751

Gnomad OTH

AF:

0.705

GnomAD2 exomes

AF:

0.652

AC:

163419

AN:

250654

AF XY:

0.659

show subpopulations

Gnomad AFR exome

AF:

0.553

Gnomad AMR exome

AF:

0.562

Gnomad ASJ exome

AF:

0.808

Gnomad EAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.757

Gnomad OTH exome

AF:

0.702

GnomAD4 exome

AF:

0.713

AC:

1041628

AN:

1461244

Hom.:

378507

Cov.:

AF XY:

0.710

AC XY:

516241

AN XY:

726918

show subpopulations

African (AFR)

AF:

0.543

AC:

18173

AN:

33472

American (AMR)

AF:

0.578

AC:

25796

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.811

AC:

21192

AN:

26130

East Asian (EAS)

AF:

0.303

AC:

12022

AN:

39694

South Asian (SAS)

AF:

0.556

AC:

47899

AN:

86218

European-Finnish (FIN)

AF:

0.734

AC:

39193

AN:

53368

Middle Eastern (MID)

AF:

0.812

AC:

4685

AN:

5768

European-Non Finnish (NFE)

AF:

0.748

AC:

830946

AN:

1111568

Other (OTH)

AF:

0.691

AC:

41722

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15719

31438

47156

62875

78594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19990

39980

59970

79960

99950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.664

AC:

101032

AN:

152056

Hom.:

34772

Cov.:

AF XY:

0.660

AC XY:

49035

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.552

AC:

22881

AN:

41466

American (AMR)

AF:

0.664

AC:

10146

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.816

AC:

2831

AN:

3470

East Asian (EAS)

AF:

0.254

AC:

1312

AN:

5172

South Asian (SAS)

AF:

0.519

AC:

2500

AN:

4814

European-Finnish (FIN)

AF:

0.740

AC:

7831

AN:

10576

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.751

AC:

51028

AN:

67968

Other (OTH)

AF:

0.700

AC:

1479

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1634

3268

4901

6535

8169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.720

Hom.:

171489

Bravo

AF:

0.657

Asia WGS

AF:

0.415

AC:

1448

AN:

3478

EpiCase

AF:

0.764

EpiControl

AF:

0.774

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary angioedema type 3 (3)

not specified (3)

not provided (2)

F12 POLYMORPHISM (1)

Factor XII deficiency disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.6

PromoterAI

0.17

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over