chr4-186286200-C-T

Position:

• chr4-186286200-C-T

Variant summary

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

The NM_000128.4(F11):​c.1481-215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 548,652 control chromosomes in the GnomAD database, including 1,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (477 hom., cov: 32)
  • Exomes 𝑓: 0.056 (783 hom.)
• Consequence: F11 NM_000128.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.28

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-186286200-C-T is Benign according to our data. Variant chr4-186286200-C-T is described in ClinVar as [Benign]. Clinvar id is 1239496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F11	NM_000128.4	c.1481-215C>T		intron_variant		ENST00000403665.7	NP_000119.1
F11-AS1	NR_033900.1	n.1133G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7	c.1481-215C>T		intron_variant		1	NM_000128.4	ENSP00000384957	P1
F11-AS1	ENST00000505103.5	n.1072G>A		non_coding_transcript_exon_variant	4/4	1
F11	ENST00000264691.4	c.176+387C>T		intron_variant		3		ENSP00000264691

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10537 AN: 151992 Hom.: 470 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0560

GnomAD4 exome AF: 0.0564 AC: 22363 AN: 396544 Hom.: 783 Cov.: 4 AF XY: 0.0575 AC XY: 12143 AN XY: 211358

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0697

Gnomad4 ASJ exome AF: 0.0823

Gnomad4 EAS exome AF: 0.0834

Gnomad4 SAS exome AF: 0.0785

Gnomad4 FIN exome AF: 0.0379

Gnomad4 NFE exome AF: 0.0457

Gnomad4 OTH exome AF: 0.0525

GnomAD4 genome AF: 0.0695 AC: 10568 AN: 152108 Hom.: 477 Cov.: 32 AF XY: 0.0696 AC XY: 5175 AN XY: 74370

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.0816

Gnomad4 EAS AF: 0.0695

Gnomad4 SAS AF: 0.0790

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0550

Alfa AF: 0.0597 Hom.: 52

Bravo AF: 0.0736

Asia WGS AF: 0.0530 AC: 183 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	Jun 19, 2021	- -
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	-0.89
CADD	Benign	0.24
DANN	Benign	0.58

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: rs2289251; hg19: chr4-187207354;