chr4-186266998-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000128.4(F11):​c.-1-138A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 679,264 control chromosomes in the GnomAD database, including 89,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21225 hom., cov: 32)
Exomes 𝑓: 0.51 ( 68310 hom. )

Consequence

F11
NM_000128.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.129
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 4-186266998-A-C is Benign according to our data. Variant chr4-186266998-A-C is described in ClinVar as [Benign]. Clinvar id is 1185146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
F11NM_000128.4 linkuse as main transcriptc.-1-138A>C intron_variant ENST00000403665.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
F11ENST00000403665.7 linkuse as main transcriptc.-1-138A>C intron_variant 1 NM_000128.4 P1P03951-1
F11ENST00000492972.6 linkuse as main transcriptc.-1-138A>C intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.525
AC:
79788
AN:
151838
Hom.:
21194
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.560
Gnomad AMI
AF:
0.520
Gnomad AMR
AF:
0.530
Gnomad ASJ
AF:
0.432
Gnomad EAS
AF:
0.622
Gnomad SAS
AF:
0.446
Gnomad FIN
AF:
0.581
Gnomad MID
AF:
0.408
Gnomad NFE
AF:
0.499
Gnomad OTH
AF:
0.521
GnomAD4 exome
AF:
0.506
AC:
266661
AN:
527306
Hom.:
68310
AF XY:
0.500
AC XY:
141823
AN XY:
283520
show subpopulations
Gnomad4 AFR exome
AF:
0.552
Gnomad4 AMR exome
AF:
0.563
Gnomad4 ASJ exome
AF:
0.430
Gnomad4 EAS exome
AF:
0.602
Gnomad4 SAS exome
AF:
0.435
Gnomad4 FIN exome
AF:
0.574
Gnomad4 NFE exome
AF:
0.497
Gnomad4 OTH exome
AF:
0.504
GnomAD4 genome
AF:
0.526
AC:
79874
AN:
151958
Hom.:
21225
Cov.:
32
AF XY:
0.526
AC XY:
39090
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.560
Gnomad4 AMR
AF:
0.530
Gnomad4 ASJ
AF:
0.432
Gnomad4 EAS
AF:
0.621
Gnomad4 SAS
AF:
0.446
Gnomad4 FIN
AF:
0.581
Gnomad4 NFE
AF:
0.499
Gnomad4 OTH
AF:
0.524
Alfa
AF:
0.437
Hom.:
2283
Bravo
AF:
0.523

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hereditary factor XI deficiency disease Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.90
DANN
Benign
0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3822057; hg19: chr4-187188152; API