Genetic Variant F11:c.-1-148_-1-147insTA (chr4-186266987-G-GAT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000128.4(F11):c.-1-148_-1-147insTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 649,868 control chromosomes in the GnomAD database, including 249,412 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.87 ( 58064 hom., cov: 0)

Exomes 𝑓: 0.88 ( 191348 hom. )

Consequence

F11
NM_000128.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.941

Publications

0 publications found

Variant links:

Genes affected

F11 (HGNC:3529): (coagulation factor XI) This gene encodes coagulation factor XI of the blood coagulation cascade. This protein is present in plasma as a zymogen, which is a unique plasma coagulation enzyme because it exists as a homodimer consisting of two identical polypeptide chains linked by disulfide bonds. During activation of the plasma factor XI, an internal peptide bond is cleaved by factor XIIa (or XII) in each of the two chains, resulting in activated factor XIa, a serine protease composed of two heavy and two light chains held together by disulfide bonds. This activated plasma factor XI triggers the middle phase of the intrisic pathway of blood coagulation by activating factor IX. Defects in this factor lead to Rosenthal syndrome, a blood coagulation abnormality. [provided by RefSeq, Jul 2008]

F11 Gene-Disease associations (from GenCC):

congenital factor XI deficiency
Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

F11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 4-186266987-G-GAT is Benign according to our data. Variant chr4-186266987-G-GAT is described in ClinVar as [Benign]. Clinvar id is 1294834.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F11	NM_000128.4 link	c.-1-148_-1-147insTA		intron_variant	Intron 1 of 14	ENST00000403665.7	NP_000119.1	P03951-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7 link	c.-1-148_-1-147insTA		intron_variant	Intron 1 of 14	1	NM_000128.4	ENSP00000384957.2		P03951-1
F11	ENST00000492972.6 link	c.-1-148_-1-147insTA		intron_variant	Intron 1 of 4	2		ENSP00000424479.1		D6RB32

Frequencies

GnomAD3 genomes

AF:

0.874

AC:

132644

AN:

151826

Hom.:

58011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.857

Gnomad AMI

AF:

0.988

Gnomad AMR

AF:

0.890

Gnomad ASJ

AF:

0.883

Gnomad EAS

AF:

0.918

Gnomad SAS

AF:

0.857

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.874

Gnomad OTH

AF:

0.891

GnomAD4 exome

AF:

0.876

AC:

436018

AN:

497924

Hom.:

191348

AF XY:

0.874

AC XY:

233005

AN XY:

266602

show subpopulations

African (AFR)

AF:

0.853

AC:

12147

AN:

14234

American (AMR)

AF:

0.885

AC:

26732

AN:

30204

Ashkenazi Jewish (ASJ)

AF:

0.881

AC:

14465

AN:

16416

East Asian (EAS)

AF:

0.928

AC:

28781

AN:

31012

South Asian (SAS)

AF:

0.842

AC:

44357

AN:

52664

European-Finnish (FIN)

AF:

0.882

AC:

30371

AN:

34434

Middle Eastern (MID)

AF:

0.896

AC:

1900

AN:

2120

European-Non Finnish (NFE)

AF:

0.875

AC:

252911

AN:

289200

Other (OTH)

AF:

0.881

AC:

24354

AN:

27640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2676

5352

8029

10705

13381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.874

AC:

132754

AN:

151944

Hom.:

58064

Cov.:

AF XY:

0.874

AC XY:

64919

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.857

AC:

35529

AN:

41448

American (AMR)

AF:

0.890

AC:

13603

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.883

AC:

3059

AN:

3466

East Asian (EAS)

AF:

0.918

AC:

4729

AN:

5152

South Asian (SAS)

AF:

0.855

AC:

4117

AN:

4814

European-Finnish (FIN)

AF:

0.880

AC:

9264

AN:

10532

Middle Eastern (MID)

AF:

0.884

AC:

258

AN:

292

European-Non Finnish (NFE)

AF:

0.874

AC:

59407

AN:

67938

Other (OTH)

AF:

0.893

AC:

1887

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

857

1714

2572

3429

4286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.872

Hom.:

7017

Bravo

AF:

0.871

Asia WGS

AF:

0.912

AC:

3171

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.94

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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4-186266987-G-GAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over