Genetic Variant NM_000128.4:c.1481-188C>T (chr4-186286227-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000128.4(F11):c.1481-188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 591,776 control chromosomes in the GnomAD database, including 41,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9788 hom., cov: 31)

Exomes 𝑓: 0.38 ( 32014 hom. )

Consequence

F11
NM_000128.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.23

Publications

87 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 links:

F11-AS1 (HGNC:27725): (F11 antisense RNA 1)

F11-AS1 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=-0.91).

BP6

Variant 4-186286227-C-T is Benign according to our data. Variant chr4-186286227-C-T is described in ClinVar as Benign. ClinVar VariationId is 760971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000128.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F11	NM_000128.4	MANE Select	c.1481-188C>T	intron	N/A	NP_000119.1	P03951-1
F11	NM_001440590.1		c.1433-188C>T	intron	N/A	NP_001427519.1
F11	NM_001440593.1		c.1480+414C>T	intron	N/A	NP_001427522.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F11	ENST00000403665.7	TSL:1 MANE Select	c.1481-188C>T	intron	N/A	ENSP00000384957.2	P03951-1
F11-AS1	ENST00000505103.5	TSL:1	n.1045G>A	non_coding_transcript_exon	Exon 4 of 4
F11	ENST00000886358.1		c.1481-319C>T	intron	N/A	ENSP00000556417.1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53736

AN:

151842

Hom.:

9777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.381

GnomAD4 exome

AF:

0.377

AC:

165709

AN:

439816

Hom.:

32014

Cov.:

AF XY:

0.373

AC XY:

87522

AN XY:

234944

show subpopulations

African (AFR)

AF:

0.255

AC:

3289

AN:

12910

American (AMR)

AF:

0.353

AC:

8593

AN:

24334

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

4804

AN:

13538

East Asian (EAS)

AF:

0.333

AC:

8919

AN:

26810

South Asian (SAS)

AF:

0.301

AC:

14787

AN:

49046

European-Finnish (FIN)

AF:

0.422

AC:

9860

AN:

23366

Middle Eastern (MID)

AF:

0.325

AC:

594

AN:

1828

European-Non Finnish (NFE)

AF:

0.401

AC:

105864

AN:

263712

Other (OTH)

AF:

0.371

AC:

8999

AN:

24272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5287

10574

15861

21148

26435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.354

AC:

53771

AN:

151960

Hom.:

9788

Cov.:

AF XY:

0.352

AC XY:

26105

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.259

AC:

10721

AN:

41430

American (AMR)

AF:

0.359

AC:

5473

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1212

AN:

3468

East Asian (EAS)

AF:

0.349

AC:

1803

AN:

5164

South Asian (SAS)

AF:

0.311

AC:

1495

AN:

4806

European-Finnish (FIN)

AF:

0.409

AC:

4305

AN:

10532

Middle Eastern (MID)

AF:

0.322

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.403

AC:

27422

AN:

67984

Other (OTH)

AF:

0.386

AC:

815

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1760

3521

5281

7042

8802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.383

Hom.:

45596

Bravo

AF:

0.347

Asia WGS

AF:

0.343

AC:

1193

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.090

(source)

DANN

Benign

0.68

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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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