ENST00000886343.1:c.-293C>G

Variant names:

• chr4-186265981-C-G
• rs3733403
• ENST00000886343.1:c.-293C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000886343.1(F11):​c.-293C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,142 control chromosomes in the GnomAD database, including 3,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3185 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: F11 ENST00000886343.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.264
• Publications: 11 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-186265981-C-G is Benign according to our data. Variant chr4-186265981-C-G is described in ClinVar as Benign. ClinVar VariationId is 348368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000886343.1. 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
	F11	NM_000128.4	MANE Select	c.-316C>G		upstream_gene	N/A	NP_000119.1
	F11	NM_001440590.1		c.-316C>G		upstream_gene	N/A	NP_001427519.1
	F11	NM_001440593.1		c.-316C>G		upstream_gene	N/A	NP_001427522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F11	ENST00000886343.1		c.-293C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000556402.1
	F11	ENST00000886351.1		c.-101C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000556410.1
	F11	ENST00000886355.1		c.-190C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000556414.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27394 AN: 152022 Hom.: 3185 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.153

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.180 AC: 27417 AN: 152142 Hom.: 3185 Cov.: 33 AF XY: 0.182 AC XY: 13514 AN XY: 74376

African (AFR) AF: 0.313 AC: 12971 AN: 41476

American (AMR) AF: 0.154 AC: 2348 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3466

East Asian (EAS) AF: 0.278 AC: 1440 AN: 5184

South Asian (SAS) AF: 0.156 AC: 752 AN: 4810

European-Finnish (FIN) AF: 0.167 AC: 1766 AN: 10594

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7536 AN: 68008

Other (OTH) AF: 0.151 AC: 318 AN: 2112

Alfa AF: 0.107 Hom.: 693

Bravo AF: 0.184

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary factor XI deficiency disease (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		0.26
PromoterAI		-0.027	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3733403; hg19: chr4-187187135;