rs1593

Positions:

• chr4-186274397-T-A
• chr4-186274397-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001354804.2(F11):​c.*118T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 1,257,504 control chromosomes in the GnomAD database, including 483,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56906 hom., cov: 33)
  • Exomes 𝑓: 0.88 (426212 hom.)
• Consequence: F11 NM_001354804.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.367

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-186274397-T-A is Benign according to our data. Variant chr4-186274397-T-A is described in ClinVar as [Benign]. Clinvar id is 1280553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F11	NM_000128.4	c.485+122T>A		intron_variant		ENST00000403665.7	NP_000119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7	c.485+122T>A		intron_variant		1	NM_000128.4	ENSP00000384957.2
F11	ENST00000492972.6	c.*118T>A		3_prime_UTR_variant	5/5	2		ENSP00000424479.1
F11	ENST00000514715.1	n.479T>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131423 AN: 152118 Hom.: 56863 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.877

GnomAD4 exome AF: 0.878 AC: 970212 AN: 1105268 Hom.: 426212 Cov.: 14 AF XY: 0.876 AC XY: 489194 AN XY: 558234

Gnomad4 AFR exome AF: 0.832

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.876

Gnomad4 EAS exome AF: 0.926

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.886

Gnomad4 NFE exome AF: 0.882

Gnomad4 OTH exome AF: 0.881

GnomAD4 genome AF: 0.864 AC: 131523 AN: 152236 Hom.: 56906 Cov.: 33 AF XY: 0.864 AC XY: 64330 AN XY: 74442

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.880

Gnomad4 OTH AF: 0.878

Alfa AF: 0.862 Hom.: 2758

Bravo AF: 0.859

Asia WGS AF: 0.891 AC: 3098 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.24
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs1593; hg19: chr4-187195551;