rs925451

chr4-186266415-G-Achr4-186266415-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000128.4(F11):c.-2+120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,060 control chromosomes in the GnomAD database, including 9,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9058 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: F11 NM_000128.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F11	NM_000128.4	c.-2+120G>A		intron_variant		ENST00000403665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F11	ENST00000403665.7	c.-2+120G>A		intron_variant		1	NM_000128.4	P1
F11	ENST00000492972.6	c.-2+120G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51289 AN: 151942 Hom.: 9041 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.363

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51339 AN: 152060 Hom.: 9058 Cov.: 33 AF XY: 0.337 AC XY: 25050 AN XY: 74324

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.367

Alfa AF: 0.375 Hom.: 14535

Bravo AF: 0.328

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.65

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: rs925451; hg19: chr4-187187569;