rs1593

Variant names:

• chr4-186274397-T-A
• rs1593
• NM_000128.4:c.485+122T>A

Your query was ambiguous. Multiple possible variants found:

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

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.485+122T>A variant causes a intron 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_000128.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.367
• Publications: 24 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 Gene-Disease associations (from GenCC):

• congenital factor XI deficiency

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
F11	NM_000128.4	c.485+122T>A		intron_variant	Intron 5 of 14	ENST00000403665.7	NP_000119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7	c.485+122T>A		intron_variant	Intron 5 of 14	1	NM_000128.4	ENSP00000384957.2
F11	ENST00000514715.1	n.479T>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
F11	ENST00000492972.6	c.*118T>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000424479.1

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

African (AFR) AF: 0.832 AC: 21288 AN: 25592

American (AMR) AF: 0.837 AC: 30112 AN: 35960

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 20433 AN: 23328

East Asian (EAS) AF: 0.926 AC: 32156 AN: 34740

South Asian (SAS) AF: 0.833 AC: 61398 AN: 73720

European-Finnish (FIN) AF: 0.886 AC: 39936 AN: 45054

Middle Eastern (MID) AF: 0.879 AC: 3174 AN: 3612

European-Non Finnish (NFE) AF: 0.882 AC: 719044 AN: 814838

Other (OTH) AF: 0.881 AC: 42671 AN: 48424

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

African (AFR) AF: 0.832 AC: 34536 AN: 41534

American (AMR) AF: 0.845 AC: 12924 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3037 AN: 3470

East Asian (EAS) AF: 0.916 AC: 4748 AN: 5182

South Asian (SAS) AF: 0.849 AC: 4100 AN: 4828

European-Finnish (FIN) AF: 0.883 AC: 9359 AN: 10604

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59822 AN: 68014

Other (OTH) AF: 0.878 AC: 1853 AN: 2110

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.24
DANN	Benign	0.36
PhyloP100		-0.37
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: rs1593; hg19: chr4-187195551;