4-186266987-G-GAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000128.4(F11):c.-1-148_-1-147insTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 649,868 control chromosomes in the GnomAD database, including 249,412 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (58064 hom., cov: 0)
  • Exomes 𝑓: 0.88 (191348 hom.)
• Consequence: F11 NM_000128.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.941

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 -10 ACMG points.

• BP6: Variant 4-186266987-G-GAT is Benign according to our data. Variant chr4-186266987-G-GAT is described in ClinVar as [Benign]. Clinvar id is 1294834.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F11	NM_000128.4	c.-1-148_-1-147insTA		intron_variant		ENST00000403665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F11	ENST00000403665.7	c.-1-148_-1-147insTA		intron_variant		1	NM_000128.4	P1
F11	ENST00000492972.6	c.-1-148_-1-147insTA		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132644 AN: 151826 Hom.: 58011 Cov.: 0

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.891

GnomAD4 exome AF: 0.876 AC: 436018 AN: 497924 Hom.: 191348 AF XY: 0.874 AC XY: 233005 AN XY: 266602

Gnomad4 AFR exome AF: 0.853

Gnomad4 AMR exome AF: 0.885

Gnomad4 ASJ exome AF: 0.881

Gnomad4 EAS exome AF: 0.928

Gnomad4 SAS exome AF: 0.842

Gnomad4 FIN exome AF: 0.882

Gnomad4 NFE exome AF: 0.875

Gnomad4 OTH exome AF: 0.881

GnomAD4 genome AF: 0.874 AC: 132754 AN: 151944 Hom.: 58064 Cov.: 0 AF XY: 0.874 AC XY: 64919 AN XY: 74236

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.890

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.893

Alfa AF: 0.872 Hom.: 7017

Bravo AF: 0.871

Asia WGS AF: 0.912 AC: 3171 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3841991; hg19: chr4-187188141;