rs5970

Variant names:

• chr4-186284147-T-C
• rs5970
• NM_000128.4:c.1191T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000128.4(F11):​c.1191T>C​(p.Gly397Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,614,012 control chromosomes in the GnomAD database, including 18,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2152 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16275 hom.)
• Consequence: F11 NM_000128.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.76
• Publications: 15 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: AR, AD, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-186284147-T-C is Benign according to our data. Variant chr4-186284147-T-C is described in ClinVar as Benign. ClinVar VariationId is 255176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 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.1191T>C	p.Gly397Gly	synonymous	Exon 11 of 15	NP_000119.1	P03951-1
	F11	NM_001440590.1		c.1143T>C	p.Gly381Gly	synonymous	Exon 11 of 15	NP_001427519.1
	F11	NM_001440593.1		c.1191T>C	p.Gly397Gly	synonymous	Exon 11 of 14	NP_001427522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F11	ENST00000403665.7	TSL:1 MANE Select	c.1191T>C	p.Gly397Gly	synonymous	Exon 11 of 15	ENSP00000384957.2	P03951-1
	F11	ENST00000886358.1		c.1191T>C	p.Gly397Gly	synonymous	Exon 11 of 16	ENSP00000556417.1
	F11	ENST00000886339.1		c.1191T>C	p.Gly397Gly	synonymous	Exon 11 of 15	ENSP00000556398.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24646 AN: 152018 Hom.: 2154 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.149 AC: 37471 AN: 251486 AF XY: 0.154

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.0458

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.145 AC: 212034 AN: 1461876 Hom.: 16275 Cov.: 33 AF XY: 0.148 AC XY: 107828 AN XY: 727238

African (AFR) AF: 0.218 AC: 7294 AN: 33480

American (AMR) AF: 0.108 AC: 4827 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4233 AN: 26136

East Asian (EAS) AF: 0.0476 AC: 1891 AN: 39700

South Asian (SAS) AF: 0.220 AC: 18958 AN: 86258

European-Finnish (FIN) AF: 0.162 AC: 8645 AN: 53418

Middle Eastern (MID) AF: 0.210 AC: 1210 AN: 5768

European-Non Finnish (NFE) AF: 0.140 AC: 155839 AN: 1111996

Other (OTH) AF: 0.151 AC: 9137 AN: 60396

GnomAD4 genome AF: 0.162 AC: 24652 AN: 152136 Hom.: 2152 Cov.: 33 AF XY: 0.163 AC XY: 12138 AN XY: 74382

African (AFR) AF: 0.209 AC: 8658 AN: 41478

American (AMR) AF: 0.123 AC: 1876 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3468

East Asian (EAS) AF: 0.0406 AC: 209 AN: 5154

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4816

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10594

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10013 AN: 68016

Other (OTH) AF: 0.151 AC: 319 AN: 2110

Alfa AF: 0.152 Hom.: 2967

Bravo AF: 0.158

Asia WGS AF: 0.130 AC: 458 AN: 3478

EpiCase AF: 0.157

EpiControl AF: 0.152

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary factor XI deficiency disease (2)
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Plasma factor XI deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.022
DANN	Benign	0.47
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs5970; hg19: chr4-187205301; COSMIC: COSV53002167; COSMIC: COSV53002167;