NM_000128.4:c.1481-215C>T

Variant names:

• chr4-186286200-C-T
• rs2289251
• NM_000128.4:c.1481-215C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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-AS1 (HGNC:27725): (F11 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F11	NM_000128.4	MANE Select	c.1481-215C>T		intron	N/A	NP_000119.1	P03951-1
	F11	NM_001440590.1		c.1433-215C>T		intron	N/A	NP_001427519.1
	F11	NM_001440593.1		c.1480+387C>T		intron	N/A	NP_001427522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F11	ENST00000403665.7	TSL:1 MANE Select	c.1481-215C>T		intron	N/A	ENSP00000384957.2	P03951-1
	F11-AS1	ENST00000505103.5	TSL:1	n.1072G>A		non_coding_transcript_exon	Exon 4 of 4
	F11	ENST00000886358.1		c.1481-346C>T		intron	N/A	ENSP00000556417.1

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

African (AFR) AF: 0.117 AC: 1353 AN: 11522

American (AMR) AF: 0.0697 AC: 1283 AN: 18414

Ashkenazi Jewish (ASJ) AF: 0.0823 AC: 999 AN: 12144

East Asian (EAS) AF: 0.0834 AC: 2110 AN: 25298

South Asian (SAS) AF: 0.0785 AC: 3530 AN: 44990

European-Finnish (FIN) AF: 0.0379 AC: 796 AN: 21024

Middle Eastern (MID) AF: 0.108 AC: 185 AN: 1706

European-Non Finnish (NFE) AF: 0.0457 AC: 10922 AN: 238890

Other (OTH) AF: 0.0525 AC: 1185 AN: 22556

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

African (AFR) AF: 0.117 AC: 4844 AN: 41484

American (AMR) AF: 0.0618 AC: 943 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3470

East Asian (EAS) AF: 0.0695 AC: 360 AN: 5182

South Asian (SAS) AF: 0.0790 AC: 381 AN: 4820

European-Finnish (FIN) AF: 0.0379 AC: 401 AN: 10578

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0461 AC: 3134 AN: 67996

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0621 Hom.: 58

Bravo AF: 0.0736

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.58
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289251; hg19: chr4-187207354;